The safety population included patients who received ≥1 dose of melflufen, daratumumab, or dexamethasone (melflufen group) and 26 patients who received daratumumab monotherapy. In the safety population, ≥1 TEAE was reported in 21 patients (96%) with melflufen, daratumumab, and dexamethasone and 22 patients (85%) with daratumumab. Overall, grade ≥3 TEAE occurred in 18 patients (82%) with melflufen, daratumumab, and dexamethasone and 14 patients (54%) with daratumumab. The most common hematologic grade ≥3 TEAE were neutropenia (melflufen group, 11 patients [50%]; daratumumab group, 3 patients [12%]), thrombocytopenia (melflufen group, 11 patients [50%]; daratumumab group, 2 patients [8%]), and anemia (melflufen group, 7 patients [32%]; daratumumab group, 5 patients [19%]). The most common non-hematologic grade ≥3 TEAE were pneumonia (melflufen group, 2 patients [9%]; daratumumab group, 2 patients [8%]) and femur fracture (melflufen group, 0 patients [0%]; daratumumab group, 2 patients [8%]); of these, 1 event (5%) of pneumonia in the melflufen group and 1 event (4%) of femur fracture in the daratumumab group were considered treatment-related TEAE by the investigator. Serious AE occurred in 6 patients (27%) with melflufen, daratumumab, and dexamethasone, and 12 patients (46%) with daratumumab. The most common serious AE (occurring in ≥4 patients overall) were anemia (melflufen group, 2 patients [9%]; daratumumab group, 3 patients [12%]) and pneumonia (melflufen group, 2 patients [9%]; daratumumab group, 2 patients [8%]). TEAE leading to treatment discontinuation occurred in 2 patients (9%) in the melflufen group (neutropenia and thrombocytopenia, N=1 each) and 4 patients (15%) in the daratumumab group (anemia, disease progression, hypercalcemia, and renal failure, N=1 each). Overall, 5 patients died on study before the crossover: 2 patients who received melflufen, daratumumab, and dexamethasone (1 due to disease progression and 1 due to unknown reasons, both >30 days after the last dose of study treatment) and 3 patients who received daratumumab (1 due to disease progression and 1 due to unknown reasons, both ≤30 days after the last dose of study treatment and 1 due to an AE [COVID-19 pneumonia], >30 days after the last dose of study treatment). In addition, one patient who crossed over to receive melflufen, daratumumab, and dexamethasone after progression on daratumumab died.

The safety population included patients who received ≥1 dose of melflufen, daratumumab, or dexamethasone (melflufen group) and 26 patients who received daratumumab monotherapy. In the safety population, ≥1 TEAE was reported in 21 patients (96%) with melflufen, daratumumab, and dexamethasone and 22 patients (85%) with daratumumab. Overall, grade ≥3 TEAE occurred in 18 patients (82%) with melflufen, daratumumab, and dexamethasone and 14 patients (54%) with daratumumab. The most common hematologic grade ≥3 TEAE were neutropenia (melflufen group, 11 patients [50%]; daratumumab group, 3 patients [12%]), thrombocytopenia (melflufen group, 11 patients [50%]; daratumumab group, 2 patients [8%]), and anemia (melflufen group, 7 patients [32%]; daratumumab group, 5 patients [19%]). The most common non-hematologic grade ≥3 TEAE were pneumonia (melflufen group, 2 patients [9%]; daratumumab group, 2 patients [8%]) and femur fracture (melflufen group, 0 patients [0%]; daratumumab group, 2 patients [8%]); of these, 1 event (5%) of pneumonia in the melflufen group and 1 event (4%) of femur fracture in the daratumumab group were considered treatment-related TEAE by the investigator. Serious AE occurred in 6 patients (27%) with melflufen, daratumumab, and dexamethasone, and 12 patients (46%) with daratumumab. The most common serious AE (occurring in ≥4 patients overall) were anemia (melflufen group, 2 patients [9%]; daratumumab group, 3 patients [12%]) and pneumonia (melflufen group, 2 patients [9%]; daratumumab group, 2 patients [8%]). TEAE leading to treatment discontinuation occurred in 2 patients (9%) in the melflufen group (neutropenia and thrombocytopenia, N=1 each) and 4 patients (15%) in the daratumumab group (anemia, disease progression, hypercalcemia, and renal failure, N=1 each). Overall, 5 patients died on study before the crossover: 2 patients who received melflufen, daratumumab, and dexamethasone (1 due to disease progression and 1 due to unknown reasons, both >30 days after the last dose of study treatment) and 3 patients who received daratumumab (1 due to disease progression and 1 due to unknown reasons, both ≤30 days after the last dose of study treatment and 1 due to an AE [COVID-19 pneumonia], >30 days after the last dose of study treatment). In addition, one patient who crossed over to receive melflufen, daratumumab, and dexamethasone after progression on daratumumab died.

Overall, at least one TEAE was reported in 13 (92.9%) and 13 (100.0%) patients in Arms A and B, respectively (Table 3). During cycle 1, 9 patients (64.3%) and 12 patients (92.3%), respectively, had at least one TEAE. Cumulatively, grade 3 or 4 AEs occurred in 12 (85.7%) and 12 (92.3%) patients, respectively, and serious AEs were reported in 5 (35.7%) and 9 (69.2%) patients, respectively. The most common any-grade AEs in Arms A and B, respectively, were thrombocytopenia (10 [71.4%]; 10 [76.9%]), neutropenia (9 [64.3%]; 9 [69.2%]), and anemia (9 [64.3%]; 7 [53.8%]). No phlebitis or local-infusion-related reactions were reported based on pre- and post-infusion inspection of the IV site, and there were no extravasations observed in Arm A or B. Similarly, VIP scores collected on Day 1 post-infusion and on Day 8 indicated that patients had healthy IV sites (VIP score of 0) with no signs of phlebitis following PVC administration of melflufen. The most common non-hematological AE was positive SARS-CoV-2 test (Arm A: 2 [14.3%]; Arm B: 4 [30.8%]). Pneumonia was the most common serious AE (Arm A: 2 [14.3%]; Arm B: 2 [15.4%]). The most common AE considered related to melflufen and/or dexamethasone by investigators was thrombocytopenia (Arm A: 10 [71.4%]; Arm B: 10 [76.9%]). AEs led to treatment discontinuation in 3 (21.4%) and 6 (46.2%) patients in Arms A and B, respectively.

Based on the safety data collected during the HORIZON trial, treatment emergent adverse events occurred in 100% of patients including 100 patients (64%) having at least 1 CTCAE grade 4 adverse effect. Hematologic grade 3 or 4 adverse effects including thrombocytopenia (76%), neutropenia (79%), anemia (43%), and infections (11%) were the most commonly reported. Other adverse effects, such as fatigue (55%), nausea (32%), diarrhea (27%), and decreased appetite (14%), were similar to other alkylating agents. Pyrexia (24%), including febrile neutropenia (5%), and respiratory tract infections (24%) were contributed to hematologic toxicities.

Melflufen plus dexamethasone was generally manageable in this heavily pretreated patient population [51]. All patients experienced ≥1 AE, most commonly hematologic AEs including thrombocytopenia (73%), neutropenia (69%), and anemia (64%). The most common non-hematologic AEs included pyrexia (40%), asthenia (31%), fatigue (29%), nausea (27%), and diarrhea (24%).

Overall, at least one TEAE was reported in 13 (92.9%) and 13 (100.0%) patients in Arms A and B, respectively (Table 3). During cycle 1, 9 patients (64.3%) and 12 patients (92.3%), respectively, had at least one TEAE. Cumulatively, grade 3 or 4 AEs occurred in 12 (85.7%) and 12 (92.3%) patients, respectively, and serious AEs were reported in 5 (35.7%) and 9 (69.2%) patients, respectively. The most common any-grade AEs in Arms A and B, respectively, were thrombocytopenia (10 [71.4%]; 10 [76.9%]), neutropenia (9 [64.3%]; 9 [69.2%]), and anemia (9 [64.3%]; 7 [53.8%]). No phlebitis or local-infusion-related reactions were reported based on pre- and post-infusion inspection of the IV site, and there were no extravasations observed in Arm A or B. Similarly, VIP scores collected on Day 1 post-infusion and on Day 8 indicated that patients had healthy IV sites (VIP score of 0) with no signs of phlebitis following PVC administration of melflufen. The most common non-hematological AE was positive SARS-CoV-2 test (Arm A: 2 [14.3%]; Arm B: 4 [30.8%]). Pneumonia was the most common serious AE (Arm A: 2 [14.3%]; Arm B: 2 [15.4%]). The most common AE considered related to melflufen and/or dexamethasone by investigators was thrombocytopenia (Arm A: 10 [71.4%]; Arm B: 10 [76.9%]). AEs led to treatment discontinuation in 3 (21.4%) and 6 (46.2%) patients in Arms A and B, respectively.

Melflufen plus dexamethasone was generally manageable in this heavily pretreated patient population [51]. All patients experienced ≥1 AE, most commonly hematologic AEs including thrombocytopenia (73%), neutropenia (69%), and anemia (64%). The most common non-hematologic AEs included pyrexia (40%), asthenia (31%), fatigue (29%), nausea (27%), and diarrhea (24%).

Overall, at least one TEAE was reported in 13 (92.9%) and 13 (100.0%) patients in Arms A and B, respectively (Table 3). During cycle 1, 9 patients (64.3%) and 12 patients (92.3%), respectively, had at least one TEAE. Cumulatively, grade 3 or 4 AEs occurred in 12 (85.7%) and 12 (92.3%) patients, respectively, and serious AEs were reported in 5 (35.7%) and 9 (69.2%) patients, respectively. The most common any-grade AEs in Arms A and B, respectively, were thrombocytopenia (10 [71.4%]; 10 [76.9%]), neutropenia (9 [64.3%]; 9 [69.2%]), and anemia (9 [64.3%]; 7 [53.8%]). No phlebitis or local-infusion-related reactions were reported based on pre- and post-infusion inspection of the IV site, and there were no extravasations observed in Arm A or B. Similarly, VIP scores collected on Day 1 post-infusion and on Day 8 indicated that patients had healthy IV sites (VIP score of 0) with no signs of phlebitis following PVC administration of melflufen. The most common non-hematological AE was positive SARS-CoV-2 test (Arm A: 2 [14.3%]; Arm B: 4 [30.8%]). Pneumonia was the most common serious AE (Arm A: 2 [14.3%]; Arm B: 2 [15.4%]). The most common AE considered related to melflufen and/or dexamethasone by investigators was thrombocytopenia (Arm A: 10 [71.4%]; Arm B: 10 [76.9%]). AEs led to treatment discontinuation in 3 (21.4%) and 6 (46.2%) patients in Arms A and B, respectively.

In the ITT population, with a median follow-up of 7.1 months in the melflufen group, the median PFS was not reached (NR) and with a median follow-up of 6.6 months in the daratumumab group, the median PFS was 4.9 months (95% CI: 3.4-NR; HR: 0.18 [95% CI: 0.05-0.65]; log-rankP=0.0032). OS was immature, with 2 events (7%) in the melflufen group and 4 events (15%) in the daratumumab group (HR: 0.47 [95% CI: 0.09-2.57]; log-rankP=0.3721) at a median follow-up of 7.6 months and 6.6 months, respectively. The ORR was 59% (95% CI: 39-78) in the melflufen group and 30% (95% CI: 14-50) in the daratumumab group (P=0.0300). More patients in the melflufen group had a complete response (CR; 1 patient [4%]vs. 0 patients [0%]) and very good partial response (VGPR; 4 patients [15%]vs. 3 patients [11%]) compared with the daratumumab group.

Efficacy endpoints were more pronounced in favor of the melflufen group compared with the daratumumab group among patients with no prior ASCT or TTP >36 months after a prior ASCT (melflufen group, N=14; daratumumab group, N=15). Median PFS was NR in the melflufen group and 3.9 months (95% CI: 1.4-4.9) in the daratumumab group (HR, 0.06 [95% CI: 0.01-0.49]; log-rank P=0.0005). Fewer OS events were reported in the melflufen group (1 event [7%] vs. 4 events [27%] in the daratumumab group; log-rank P=0.0369). The ORR was 64% (95% CI: 35-87) in the melflufen group and 13% (95% CI: 2-41) in the daratumumab group (P=0.0055). More patients in the melflufen group had a CR (1 patient [7%] vs. 0 patients [0%]) or VGPR (2 patients [14%] vs. 1 patient [7%]) compared with the daratumumab group.

Overall, the safety profile of melflufen plus dexamethasone in the alkylator-refractory group was consistent between treatment arms (Table 2). In the melflufen and pomalidomide arms, respectively, the frequency of treatment-emergent adverse events (TEAEs; 99% vs. 97%), Grade 3 or 4 TEAEs (85% vs. 82%), serious TEAEs (49% vs. 53%), and fatal TEAEs (19% vs. 16%) were similar (Table 2). However, melflufen compared with pomalidomide saw more dose modifications (76% vs. 67%) and dose reductions (47% vs. 14%), comparable dose delays (57% vs. 51%) but less treatment discontinuation (27% vs. 34%). When comparing patients refractory and not refractory to prior alkylators, rates of TEAEs were generally comparable except for slightly lower rates of serious and fatal TEAEs observed in patients not refractory to alkylators. Among Grade 3 or 4 TEAEs of special interest, melflufen saw more thrombocytopenia (73% vs. 14%), neutropenia (65% vs. 55%), and leukopenia or white blood cell decrease (14% vs. 3%), but less infection (15% vs. 26%), than pomalidomide. Notably, melflufen compared with pomalidomide saw a longer median time to dose reduction (106 days [range, 28-443] vs. 47 days [range, 28-225]), Grade 3 or 4 thrombocytopenia (52 days [range, 15-451] vs. 19 days [range, 8-91]), and Grade 3 or 4 neutropenia (36 days [range, 8-561] vs. 22 days [range, 8-470]).

Overall, at least one TEAE was reported in 13 (92.9%) and 13 (100.0%) patients in Arms A and B, respectively (Table 3). During cycle 1, 9 patients (64.3%) and 12 patients (92.3%), respectively, had at least one TEAE. Cumulatively, grade 3 or 4 AEs occurred in 12 (85.7%) and 12 (92.3%) patients, respectively, and serious AEs were reported in 5 (35.7%) and 9 (69.2%) patients, respectively. The most common any-grade AEs in Arms A and B, respectively, were thrombocytopenia (10 [71.4%]; 10 [76.9%]), neutropenia (9 [64.3%]; 9 [69.2%]), and anemia (9 [64.3%]; 7 [53.8%]). No phlebitis or local-infusion-related reactions were reported based on pre- and post-infusion inspection of the IV site, and there were no extravasations observed in Arm A or B. Similarly, VIP scores collected on Day 1 post-infusion and on Day 8 indicated that patients had healthy IV sites (VIP score of 0) with no signs of phlebitis following PVC administration of melflufen. The most common non-hematological AE was positive SARS-CoV-2 test (Arm A: 2 [14.3%]; Arm B: 4 [30.8%]). Pneumonia was the most common serious AE (Arm A: 2 [14.3%]; Arm B: 2 [15.4%]). The most common AE considered related to melflufen and/or dexamethasone by investigators was thrombocytopenia (Arm A: 10 [71.4%]; Arm B: 10 [76.9%]). AEs led to treatment discontinuation in 3 (21.4%) and 6 (46.2%) patients in Arms A and B, respectively.

Overall, at least one TEAE was reported in 13 (92.9%) and 13 (100.0%) patients in Arms A and B, respectively (Table 3). During cycle 1, 9 patients (64.3%) and 12 patients (92.3%), respectively, had at least one TEAE. Cumulatively, grade 3 or 4 AEs occurred in 12 (85.7%) and 12 (92.3%) patients, respectively, and serious AEs were reported in 5 (35.7%) and 9 (69.2%) patients, respectively. The most common any-grade AEs in Arms A and B, respectively, were thrombocytopenia (10 [71.4%]; 10 [76.9%]), neutropenia (9 [64.3%]; 9 [69.2%]), and anemia (9 [64.3%]; 7 [53.8%]). No phlebitis or local-infusion-related reactions were reported based on pre- and post-infusion inspection of the IV site, and there were no extravasations observed in Arm A or B. Similarly, VIP scores collected on Day 1 post-infusion and on Day 8 indicated that patients had healthy IV sites (VIP score of 0) with no signs of phlebitis following PVC administration of melflufen. The most common non-hematological AE was positive SARS-CoV-2 test (Arm A: 2 [14.3%]; Arm B: 4 [30.8%]). Pneumonia was the most common serious AE (Arm A: 2 [14.3%]; Arm B: 2 [15.4%]). The most common AE considered related to melflufen and/or dexamethasone by investigators was thrombocytopenia (Arm A: 10 [71.4%]; Arm B: 10 [76.9%]). AEs led to treatment discontinuation in 3 (21.4%) and 6 (46.2%) patients in Arms A and B, respectively.

The phase I arm established 40 mg of melflufen as the maximum tolerated dose in combination with dexamethasone. The phase II arm found an overall response rate (ORR) of 31% (14 patients) and clinical benefit rate, defined as first occurrence of disease response including minimal response or better, of 49% (22 patients) in the melflufen and dexamethasone group compared with an ORR of 8% (1 patient) and clinical benefit rate of 23% (3 patients) in the melflufen group. Based on these findings, melflufen 40 mg plus dexamethasone 40 mg was deemed a feasible treatment regimen for relapsed and refractory multiple myeloma and appropriate to proceed to a larger phase II trial.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In Arm A, 4 of the 14 patients achieved an overall response (ORR 28.6% [95% CI: 8.4-58.1]) including 1 patient with CR, and the CBR was 57.1% (95% CI: 28.9-82.3). In Arm B, 1 of the 13 patients achieved an overall response (ORR 7.7% [95% CI: 0.2-36.0]), consisting of a PR, and the CBR was 15.4% (95% CI: 1.9-45.4). In the overall study population, 5 patients had an overall response (ORR 18.5% [95% CI: 6.3-38.1]). DOR data were insufficient to evaluate due to early termination of the study, the low number of patient events (1 in Arm A, 0 in Arm B), and the limited number of responses. Based on the 5 patients who had a response of PR or better at study termination (4 in Arm A, 1 in Arm B), the median TTR was 2.4 months in Arm A, 5.1 months in Arm B, and 2.6 months overall. Based on the 8 and 5 progression events in Arm A and Arm B, respectively, the median TTP was 5.8 months and 4.8 months, respectively, with a median TTP of 5.8 months in the overall population. The median PFS was 5.2 months (95% CI: 2.7 to not evaluable) and 2.9 months (95% CI: 1.5-4.6) in Arms A and B, respectively. For the overall study population, median PFS was 3.7 months (95% CI: 2.7-5.8).

Efficacy endpoints were more pronounced in favor of the melflufen group compared with the daratumumab group among patients with no prior ASCT or TTP >36 months after a prior ASCT (melflufen group, N=14; daratumumab group, N=15). Median PFS was NR in the melflufen group and 3.9 months (95% CI: 1.4-4.9) in the daratumumab group (HR, 0.06 [95% CI: 0.01-0.49]; log-rank P=0.0005). Fewer OS events were reported in the melflufen group (1 event [7%] vs. 4 events [27%] in the daratumumab group; log-rank P=0.0369). The ORR was 64% (95% CI: 35-87) in the melflufen group and 13% (95% CI: 2-41) in the daratumumab group (P=0.0055). More patients in the melflufen group had a CR (1 patient [7%] vs. 0 patients [0%]) or VGPR (2 patients [14%] vs. 1 patient [7%]) compared with the daratumumab group.

In the ITT population, with a median follow-up of 7.1 months in the melflufen group, the median PFS was not reached (NR) and with a median follow-up of 6.6 months in the daratumumab group, the median PFS was 4.9 months (95% CI: 3.4-NR; HR: 0.18 [95% CI: 0.05-0.65]; log-rankP=0.0032). OS was immature, with 2 events (7%) in the melflufen group and 4 events (15%) in the daratumumab group (HR: 0.47 [95% CI: 0.09-2.57]; log-rankP=0.3721) at a median follow-up of 7.6 months and 6.6 months, respectively. The ORR was 59% (95% CI: 39-78) in the melflufen group and 30% (95% CI: 14-50) in the daratumumab group (P=0.0300). More patients in the melflufen group had a complete response (CR; 1 patient [4%]vs. 0 patients [0%]) and very good partial response (VGPR; 4 patients [15%]vs. 3 patients [11%]) compared with the daratumumab group.

In Arm A, 4 of the 14 patients achieved an overall response (ORR 28.6% [95% CI: 8.4-58.1]) including 1 patient with CR, and the CBR was 57.1% (95% CI: 28.9-82.3). In Arm B, 1 of the 13 patients achieved an overall response (ORR 7.7% [95% CI: 0.2-36.0]), consisting of a PR, and the CBR was 15.4% (95% CI: 1.9-45.4). In the overall study population, 5 patients had an overall response (ORR 18.5% [95% CI: 6.3-38.1]). DOR data were insufficient to evaluate due to early termination of the study, the low number of patient events (1 in Arm A, 0 in Arm B), and the limited number of responses. Based on the 5 patients who had a response of PR or better at study termination (4 in Arm A, 1 in Arm B), the median TTR was 2.4 months in Arm A, 5.1 months in Arm B, and 2.6 months overall. Based on the 8 and 5 progression events in Arm A and Arm B, respectively, the median TTP was 5.8 months and 4.8 months, respectively, with a median TTP of 5.8 months in the overall population. The median PFS was 5.2 months (95% CI: 2.7 to not evaluable) and 2.9 months (95% CI: 1.5-4.6) in Arms A and B, respectively. For the overall study population, median PFS was 3.7 months (95% CI: 2.7-5.8).

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

Based on the safety data collected during the HORIZON trial, treatment emergent adverse events occurred in 100% of patients including 100 patients (64%) having at least 1 CTCAE grade 4 adverse effect. Hematologic grade 3 or 4 adverse effects including thrombocytopenia (76%), neutropenia (79%), anemia (43%), and infections (11%) were the most commonly reported. Other adverse effects, such as fatigue (55%), nausea (32%), diarrhea (27%), and decreased appetite (14%), were similar to other alkylating agents. Pyrexia (24%), including febrile neutropenia (5%), and respiratory tract infections (24%) were contributed to hematologic toxicities.

Based on the safety data collected during the HORIZON trial, treatment emergent adverse events occurred in 100% of patients including 100 patients (64%) having at least 1 CTCAE grade 4 adverse effect. Hematologic grade 3 or 4 adverse effects including thrombocytopenia (76%), neutropenia (79%), anemia (43%), and infections (11%) were the most commonly reported. Other adverse effects, such as fatigue (55%), nausea (32%), diarrhea (27%), and decreased appetite (14%), were similar to other alkylating agents. Pyrexia (24%), including febrile neutropenia (5%), and respiratory tract infections (24%) were contributed to hematologic toxicities.

Melflufen plus dexamethasone was generally manageable in this heavily pretreated patient population [51]. All patients experienced ≥1 AE, most commonly hematologic AEs including thrombocytopenia (73%), neutropenia (69%), and anemia (64%). The most common non-hematologic AEs included pyrexia (40%), asthenia (31%), fatigue (29%), nausea (27%), and diarrhea (24%).

Overall, at least one TEAE was reported in 13 (92.9%) and 13 (100.0%) patients in Arms A and B, respectively (Table 3). During cycle 1, 9 patients (64.3%) and 12 patients (92.3%), respectively, had at least one TEAE. Cumulatively, grade 3 or 4 AEs occurred in 12 (85.7%) and 12 (92.3%) patients, respectively, and serious AEs were reported in 5 (35.7%) and 9 (69.2%) patients, respectively. The most common any-grade AEs in Arms A and B, respectively, were thrombocytopenia (10 [71.4%]; 10 [76.9%]), neutropenia (9 [64.3%]; 9 [69.2%]), and anemia (9 [64.3%]; 7 [53.8%]). No phlebitis or local-infusion-related reactions were reported based on pre- and post-infusion inspection of the IV site, and there were no extravasations observed in Arm A or B. Similarly, VIP scores collected on Day 1 post-infusion and on Day 8 indicated that patients had healthy IV sites (VIP score of 0) with no signs of phlebitis following PVC administration of melflufen. The most common non-hematological AE was positive SARS-CoV-2 test (Arm A: 2 [14.3%]; Arm B: 4 [30.8%]). Pneumonia was the most common serious AE (Arm A: 2 [14.3%]; Arm B: 2 [15.4%]). The most common AE considered related to melflufen and/or dexamethasone by investigators was thrombocytopenia (Arm A: 10 [71.4%]; Arm B: 10 [76.9%]). AEs led to treatment discontinuation in 3 (21.4%) and 6 (46.2%) patients in Arms A and B, respectively.

Based on the safety data collected during the HORIZON trial, treatment emergent adverse events occurred in 100% of patients including 100 patients (64%) having at least 1 CTCAE grade 4 adverse effect. Hematologic grade 3 or 4 adverse effects including thrombocytopenia (76%), neutropenia (79%), anemia (43%), and infections (11%) were the most commonly reported. Other adverse effects, such as fatigue (55%), nausea (32%), diarrhea (27%), and decreased appetite (14%), were similar to other alkylating agents. Pyrexia (24%), including febrile neutropenia (5%), and respiratory tract infections (24%) were contributed to hematologic toxicities.

Melflufen plus dexamethasone was generally manageable in this heavily pretreated patient population [51]. All patients experienced ≥1 AE, most commonly hematologic AEs including thrombocytopenia (73%), neutropenia (69%), and anemia (64%). The most common non-hematologic AEs included pyrexia (40%), asthenia (31%), fatigue (29%), nausea (27%), and diarrhea (24%).

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

Based on the safety data collected during the HORIZON trial, treatment emergent adverse events occurred in 100% of patients including 100 patients (64%) having at least 1 CTCAE grade 4 adverse effect. Hematologic grade 3 or 4 adverse effects including thrombocytopenia (76%), neutropenia (79%), anemia (43%), and infections (11%) were the most commonly reported. Other adverse effects, such as fatigue (55%), nausea (32%), diarrhea (27%), and decreased appetite (14%), were similar to other alkylating agents. Pyrexia (24%), including febrile neutropenia (5%), and respiratory tract infections (24%) were contributed to hematologic toxicities.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.

In the safety population, the median duration of treatment was 58 months (IQR 28-111) in the melflufen group and 51 months (26-92) in the pomalidomide group. Patients received a median of five treatment cycles in each treatment group (melflufen: IQR 3-11; pomalidomide: IQR 3-10). The most common treatment-emergent adverse events by preferred term and treatment group are summarised in table 2 and the appendix (pp 23-31 ), and disaggregated by sex in the appendix (pp 32-35 ). The most common haematological grade 3 or 4 events in the melflufen and pomalidomide groups were neutropenia (123 [54%] of 228 vs 102 [41%] of 246), thrombocytopenia (143 [63%] vs 26 [11%]), and anaemia (97 [43%] vs 44 [18%]), and the most common grade 3 or 4 non-haematological event was pneumonia (ten [4%] vs 20 [8%]). The most common grade 3 or 4 treatment-related treatment-emergent adverse events in the melflufen and pomalidomide groups were thrombocytopenia (138 [61%] vs 22 [9%]), neutropenia (122 [54%] vs 97 [39%]), anaemia (87 [38%] vs 25 [10%] ). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) patients in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]), and were considered to be treatment related in 42 (18%) in the melflufen group and 52 (21%) in the pomalidomide group. In the safety population, 106 (46%) patients in the melflufen group and 106 (43%) patients in the pomalidomide group died overall. 23 (10%) patients in the melflufen group and 33 (13%) in the pomalidomide group died within 30 days of receiving their last dose of study drug; 83 (36%) in the melflufen group and 73 (30%), in the pomalidomide group died 30 days after having received their last dose of study medication. Additionally, 13 patients who were randomly assigned but not treated died (assigned to melflufen group, 11 [61%] of 18; pomalidomide group, two [67%] of three). In an exploratory analysis of prespecified subgroups of clinical relevance in the ITT population, progression-free survival data favoured melflufen in most subgroups, including patients aged 75 years and older (HR 043 [95% CI 024-076]; p=00031) and patients without a previous autologous HSCT (HR 059 [044-079]; p=00004). By contrast, overall survival data favoured pomalidomide in patients younger than 65 years (HR 171 [95% CI 109-269]; p=0019) and those with a previous autologous HSCT (HR 161 [109-240]; p=0017). Age and previous autologous HSCT remained significant prognostic factors on the basis of an interaction test.