Abstract Topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Background: Belamaf, an antibody-drug conjugate targeting B-cell maturation antigen, induces cell death by direct cell kill and immune-mediated mechanisms. The Phase 3, open-label, randomized, multicenter DREAMM-3 trial (NCT04162210) evaluated belamaf monotherapy vs Pd in adult pts with RRMM at second relapse (3L+) or later.
Aims: To evaluate changes from baseline (BL) in disease symptoms and health-related quality of life as well as pt-reported tolerability of belamaf vs Pd in DREAMM-3.
Methods: Pts were randomized (2:1) to receive belamaf or Pd and completed electronic pt-reported outcome (PRO) measures at BL and every 3 weeks during treatment (tx). Key domains of health, including fatigue, physical functioning, and global health were evaluated using the EORTC 30-item Core Module (QLQ-C30). MM-specific pain was evaluated with the disease symptoms domain of the EORTC Multiple Myeloma module (QLQ-MY20). The impact of potential ocular symptoms on vision-related functioning (VRF) was evaluated with the Ocular Surface Disease Index (OSDI). Overall tolerability and pt-reported adverse events (AEs) were assessed by FACT-GP5 and PRO-CTCAE. For EORTC measures, mean change from BL was compared between tx groups (grps) over time with mixed models for repeated measures. Proportions of pts with meaningful change in EORTC scores (≥10-point change) and VRF scores (≥12.5-point change) were also reported by visit.
Results: Among 287 pts (belamaf n=192, Pd n=95), compliance with PRO assessments was 75–90% in both grps across most study visits. The belamaf grp reported small mean improvements from BL in fatigue scores, with statistically significantly greater improvements vs Pd at Week (W) 13, W19, and W40. Higher proportions of pts in the belamaf grp (~40–60%) reported meaningful improvement in fatigue vs Pd (~25–40%) across visits. There were no statistically significant between-grp differences in mean scores for other EORTC domains. Mean scores for global health status and physical functioning remained stable or improved throughout the study in both grps, with belamaf demonstrating increasingly larger improvements from W37. Meaningful improvement in global health scores was seen in 29% of pts on belamaf at W4, increasing to 53% at later timepoints. Both tx grps reported small mean improvements from BL in disease pain, with 27–58% of pts on belamaf achieving meaningful improvement at each visit. Deterioration in VRF was observed by W7 with belamaf; 67% of pts showed ≥1 instance of meaningful deterioration vs 49% on Pd. While 31% of pts on belamaf reported ≥1 instance of “severe” or “very severe” blurred vision (PRO-CTCAE) vs 8% on Pd, belamaf was well tolerated overall with >80% of pts in both grps reporting either none, mild, or infrequent AEs at each visit. Most pts on belamaf (>70%) reported feeling “not at all” or only “a little” bothered by tx side effects across visits (FACT-GP5). Comparable tolerability was observed in the Pd grp.
Summary/Conclusion: Pts receiving belamaf vs Pd showed meaningful improvement in fatigue, a difficult-to-manage symptom of RRMM. Pts also showed small mean improvements in MM-associated pain across both grps. Despite ocular AEs, physical functioning and global health status for pts on belamaf improved over time. Future PRO work will focus on time-to-event and responder-based analyses. Overall, DREAMM-3 PRO data demonstrate that belamaf monotherapy is a well-tolerated tx option with a positive impact on important health outcomes for pts with 3L+ RRMM, particularly fatigue.
Funding: GSK (Study 207495)
Figure. Change from baseline in EORTC QLQ-C30 fatigue domain score, by visit
Keywords: Patient reported outcomes, Multiple myeloma, Quality of life