DREAMM-7 study of belantamab mafodotin plus bortezomib and dexamethasone (BVd) vs daratumumab plus bortezomib and dexamethasone (DVd) in relapsed/refractory multiple myeloma (RRMM): A subgroup analysis in patients (pts) with high-risk cytogenetic (HRC) features.

Abstract

7546 Background: In DREAMM-7 (NCT04246047), BVd exhibited a significant improvement in the risk of progression or death vs DVd in pts with RRMM who had ≥1 prior line of treatment. In a post hoc analysis (Mateos et al; ASCO 2024) of pts with ≥1 HRC abnormality (HRCA), including t(4;14), t(14;16), and 17p13del, more pts had deep responses (defined as complete response [CR] or better) with BVd (45%; 95% CI, 32.6%-57.4%) than with DVd (13%; 95% CI, 6.1%-23.3%). Up to 70% of pts at early relapse have amp1q, which confers an increased risk of disease progression. Here we present an updated post hoc efficacy analysis in pts with HRCA, including amp1q. Methods: Pts were randomized 1:1 to BVd or DVd as previously reported. For this analysis, pts with HRC were defined as those having ≥1 HRCA, including t(4;14), t(14;16), t(14;20), 17p13del, and amp1q (defined as ≥4 copies of chromosome 1q21). Descriptive statistics were used to summarize results, with 95% exact CI. Hazard ratios (HRs) for progression-free survival (PFS) were estimated using the Cox model, with 95% CI based on the Brookmeyer-Crowley method. Results: The ITT population included 494 pts: BVd, n=243; DVd, n=251. In the BVd arm, 122/243 pts (50%) had HRC, of which 41 (17%) had t(4;14), 8 (3%) had t(14;16), 1 (0.4%) had t(14;20), 30 (12%) had 17p13del, and 94 (39%) had amp1q. In the DVd arm, 115/251 (46%) had HRC, of which 42 (17%) had t(4;14), 6 (2%) had t(14;16), 1 (0.4%) had t(14;20), 35 (14%) had 17p13del, and 79 (31%) had amp1q. Median PFS in pts with ≥1 HRCA was 33.2 mo (95% CI, 20.1 mo-not reached) with BVd vs 11.1 mo (95% CI, 9.0-15.1 mo) with DVd (HR, 0.40; 95% CI, 0.27-0.59), and 18-mo PFS rates were 61% and 38%, respectively. PFS benefit favored BVd across subgroups (HR [95% CI]): t(4;14), 0.36 [0.19-0.67]; 17p13del, 0.25 [0.11-0.61]; amp1q, 0.48 [0.31-0.73]; t (14;16) and t(14;20) were not analyzed due to low numbers. In pts with ≥1 HRCA, overall response rate was 81% (n=99; 95% CI, 73.1%-87.7%) with BVd and 69% (n=79; 95% CI, 59.4%-77.0%) with DVd; more pts achieved ≥CR with BVd than with DVd (Table). The benefit was maintained across subgroups. Conclusions: In pts with RRMM and ≥1 HRCA, PFS benefit favored BVd vs DVd, and BVd demonstrated a higher rate of deep response. Current outcomes in pts with HRC features are suboptimal, and these data support BVd as a potential standard-of-care regimen in these pts with high unmet need. Clinical trial information: NCT04246047 . Patients achieving ≥CR in HRC Groups n/N (%); 95% CI BVd DVd t (4;14) 20/41 (49); 32.9-64.9 6/42 (14); 5.4-28.5 t (14;16) 1/8 (13); 0.3-52.7 0/6; 0-45.9 17p13del 11/30 (37); 19.9-56.1 4/35 (11); 3.2-26.7 amp1q 31/94 (33); 23.6-43.4 16/79 (20); 12.0-30.8 ≥1 HRCA 48/122 (39); 30.6-48.6 20/115 (17); 11.0-25.6