S199: a phase 3, open-label, randomized study evaluating the efficacy and safety of single agent belantamab mafodotin vs pomalidomide plus dexamethasone in relapsed/refractory multiple myeloma (dreamm-3)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Belantamab mafodotin (belamaf), an antibody-drug conjugate targeting B-cell maturation antigen, induces cell death by direct cell killing and immune-mediated mechanisms. The DREAMM-2 trial (NCT03525678) showed rapid, deep, and durable responses to belamaf monotherapy in patients with relapsed or refractory multiple myeloma (RRMM). Aims: This Phase 3, open-label, randomized, multicenter DREAMM-3 trial (NCT04162210) evaluated belamaf monotherapy vs. pomalidomide plus low-dose dexamethasone (Pd) in adult patients with RRMM at second relapse (third line) or later. Methods: Patients were randomized (2:1) to belamaf 2.5 mg/kg every 3 weeks (Q3W) or Pd (pomalidomide 4 mg orally [PO] daily on days 1–21 of each 28-day cycle; dexamethasone, 40 mg PO [20 mg if >75 years old]) weekly. The primary endpoint was progression-free survival (PFS). Results: Three-hundred twenty-five patients were enrolled (belamaf n=218, Pd n=107). Median (range) age was 68 (38–90) years; 57% were male. Median (range) duration of exposure for belamaf was 4.1 (0.4, 22.9) months and 5.3 (0.4, 24.0) months for Pd. Median (range) duration of follow-up was 11.5 (0.6, 24.2) months for belamaf and 10.8 (0.0, 26.4) months for Pd. Median [range] PFS was longer for belamaf (11.2 [6.4, 14.5] months) vs. Pd (7.0 [4.6, 10.6] months). There was no statistically significant difference in PFS between the two treatment groups, (Hazard Ratio [HR] 1.03 [95% CI: 0.72, 1.47]), based on the stratified Cox model (p=0.558). Belamaf induced deeper responses vs. Pd (Table). Median duration of response was more durable for belamaf than for Pd (Table). At 12 months, the probability (95% CI) of maintaining the response was 0.768 (0.641, 0.854) for belamaf and 0.484 (0.258, 0.679) for Pd. Median progression-free survival on subsequent line of therapy (PFS2) was 18.7 months (95% CI 14.5, Not Reached [NR]) for belamaf and 12.7 months (9.3, 21.1) for Pd. The PFS2 rate at 6 months was 73% for belamaf and 76% for Pd. Overall survival (OS) data were immature (37.5% overall maturity) at the time of this analysis; median OS was 21.2 months (95% CI 18.7, NR) for belamaf and 21.1 months (15.1, NR) for Pd (HR 1.14 [95% CI 0.77, 1.68]; p=0.746). Adverse events (AEs) were reported in 97% and 93% of patients (Table). The safety profile was consistent with previous reports for belamaf and Pd. Summary/Conclusion: Belamaf monotherapy did not demonstrate PFS superiority when compared to a doublet (Pd). However, median PFS was longer for belamaf monotherapy and belamaf induced deeper, more durable responses than Pd. No new safety signals were observed. Subgroup analyses and patient reported outcomes will be presented. Belamaf continues to be investigated in combination with established and novel agents. Funding: GSK (Study 207495); drug linker technology licensed from Seagen Inc.; mAb produced using POTELLIGENT Technology licensed from BioWa. This abstract was previously submitted to the American Society of Clinical Oncology (ASCO) Annual Meeting, June 2–6, 2023, and is submitted on behalf of the original authors with their permission. ©2023 American Society of Clinical Oncology, Inc. Reused with permission. All rights reserved.Keywords: Relapse, Refractory, B-cell maturation antigen, Multiple myeloma