Background: The phase 3 OCEAN study (OP-103; NCT03151811 ) met its primary endpoint; melphalan flufenamide (melflufen) + dex showed superior progression-free survival vs pom+dex in patients with RRMM refractory to lenalidomide, but overall survival (secondary endpoint) numerically favored pom+dex (Schjesvold FH, et al. Lancet Haematol . 2022;9[2]:e98-e110). Hematologic adverse events (AEs) were more frequent with melflufen+dex, but grade 3/4 infections were more common with pom+dex. Melflufen+dex was approved in Europe for the treatment of patients with ≥3 prior lines of therapy and triple—class refractory RRMM; if patients had prior autologous stem cell transplant (ASCT), time to progression (TTP) must have been >36 months.
RRMM is associated with severe symptoms, of which pain, fatigue, physical functioning, and emotional functioning have been strongly linked to impairments in health-related quality of life (HRQoL) for patients. Because HRQoL is known to deteriorate with each subsequent line of therapy, treatment goals should include preserving or even improving HRQoL (Engelhardt M, et al. Clin Lymphoma Myeloma Leuk . 2020;21[2]:e160-e175).
Objective: To evaluate functional status and well-being based on PRO assessments in patients receiving treatment with either melflufen+dex or pom+dex in the OCEAN study. Secondly, to assess PROs in the subgroup of patients with TTP >36 months after an ASCT or had no prior ASCT to understand whether results are generalizable to patients in the global target population.
Methods: EORTC QLQ-C30, EORTC QLQ-MY20 and EQ-5D-3L were included in the OCEAN trial beginning with protocol version 4.1 and assessed before treatment in each cycle. Mean scores per cycle and change from baseline to cycle 6 were analyzed for Global Health Status/QoL, Physical Functioning, Emotional Functioning, Pain, Fatigue, Disease Symptoms, and Side Effects of Treatment. Within the melflufen+dex arm, the target population was compared vs the non–target population (ie, patients with TTP <36 months after an ASCT).
Results: Baseline characteristics were generally well matched between patients reporting PROs (n=158) and the overall study population (N=495). Overall, mean baseline scores before treatment were similar between melflufen+dex and pom+dex treatment groups: 63.8 vs 64.3 in Global Health Status/QoL, 72.4 vs 74.2 in Physical Functioning, 81.0 vs 79.8 in Emotional Functioning, 35.1 vs 32.6 in Fatigue, 30.2 vs 28.7 in Pain, 24.7 vs 22.6 in Disease Symptoms, 16.1 vs 16.1 in Side Effects of Treatment, and 64.0 vs 66.9 for the EQ-5D-3L VAS, respectively. Mean scores remained generally constant between baseline and follow-up timepoints (Figure). Mean baseline scores before treatment with melflufen+dex were similar between the target population and the non–target population groups: 65.3 vs 61.9 in Global Health Status/QoL, 73.2 vs 71.5 in Physical Functioning, 83.3 vs 78.0 in Emotional Functioning, 30.7 vs 40.7 in Fatigue, 26.2 vs 35.4 in Pain, 23.0 vs 27.1 in Disease Symptoms, 15.9 vs 16.3 in Side Effects of Treatment, and 64.8 vs 62.8 for the EQ-5D-3L VAS, respectively. Despite small patient numbers (n=44), the target population group showed a similar trend to that of the overall population.
Conclusion: Given the negative impact of treatment-related AEs on HRQoL in RRMM, results from OCEAN are encouraging. HRQoL was maintained throughout treatment with melflufen+dex, including in the target population, and was similar to that with pom+dex.
