DREAMM-8 study of belantamab mafodotin plus pomalidomide and dexamethasone (BPd) vs pomalidomide plus bortezomib and dexamethasone (PVd) in relapsed/refractory multiple myeloma (RRMM): A subgroup analysis in patients with high-risk cytogenetic features.

Abstract

7533 Background: In DREAMM-8 (NCT04484623), BPd demonstrated a significant improvement in the risk of progression or death vs PVd in patients (pts) with RRMM who received ≥1 prior line of therapy, including lenalidomide. Pts with high-risk cytogenetic abnormalities (HRCAs) have a poor prognosis and need more efficacious treatments. Here we present a subgroup analysis in pts with HRCAs. Methods: Pts were randomized 1:1 to BPd (28-day cycles) or PVd (21-day cycles). Pts were treated until progressive disease, unacceptable toxicity, or death. Efficacy assessments occurred every 4 weeks. Pts with HRCAs were defined as having ≥1 of the following: t(4;14), t(14;16), amp1q, and del(17p13). Descriptive statistics were used to summarize the results, along with 95% exact CIs. Hazard ratios (HRs) for progression-free survival (PFS) were estimated using the Cox model, with 95% CIs based on the Brookmeyer-Crowley method. Results: The intention-to-treat population included 302 pts: 155 in the BPd arm and 147 in the PVd arm. In the BPd arm, 68 of 155 (44%) pts had HRCAs; of them, 23 (15%) had t(4;14), 7 (5%) had t(14;16), 32 (21%) had del(17p13), and 40 (26%) had amp1q. In the PVd arm, 60 of 147 (41%) had HRCAs; of them, 20 (14%) had t(4;14), 11 (7%) had t(14;16), 26 (18%) had del(17p13), and 33 (22%) had amp1q. Median PFS in pts with ≥1 HRCA was 21.1 mo (95% CI, 13.5 mo-NR) with BPd vs 9.2 mo (95% CI, 6.5-14.8 mo) with PVd (HR, 0.58; 95% CI, 0.36-0.95); 18-mo PFS rates were 53% and 33%, respectively. PFS benefit favored BPd across HRCA subgroups (HR [95% CI]: t(14;14), 0.74 [0.31-1.76]; del(17p13), 0.45 [0.22-0.92]; and amp1q, 0.49 [0.24-1.03]). In pts with ≥1 HRCA, overall response rate (ORR) was higher with BPd (n=52; 76%; 95% CI, 64.6%-85.9%) than PVd (n=39; 65%; 95% CI, 51.6%-76.9%), and more pts achieved ≥ complete response with BPd (Table). Benefit was maintained across HRCA subgroups. Conclusions: In pts with RRMM with HRC features, BPd demonstrated clinically meaningful PFS benefit, higher ORR, and a higher rate of deep responses vs PVd. These data support the potential use of BPd as a standard-of-care regimen in this key pt population with a high unmet need. Clinical trial information: NCT04484623 . Patients achieving ≥CR in HRC groups n/N (%); 95% CI BPd PVd t(4;14) 9/23 (39); 19.7-61.5 5/20 (25); 8.7-49.1 t(14;16) 3/7 (43); 9.9-81.6 2/11 (18); 2.3-51.8 del(17p13) 11/32 (34); 18.6-53.2 0/26; 0-13.2 amp1q 17/40 (43); 27.0-59.1 3/33 (9); 1.9-24.3 ≥1 HRCA 29/68 (43); 30.7-55.2 9/60 (15); 7.1-26.6