Functional high-risk Relapsed/Refractory multiple myeloma (RRMM) outcomes with belantamab mafodotin (belamaf): Dreamm-7 and dreamm-8 subgroup analysis

Abstract

Abstract Background: There is a significant need for effective and well-tolerated therapies for patients (pts) with functional high-risk (FHR) MM. In DREAMM-7 (D7; NCT04246047), belamaf, bortezomib, and dexamethasone (BVd) demonstrated significant PFS and OS benefit vs daratumumab-Vd (DVd) in pts with RRMM with ≥1 prior line of therapy (LOT). In DREAMM-8 (D8; NCT04484623), belamaf, pomalidomide, and dexamethasone (BPd) demonstrated a significant PFS benefit vs PVd in pts with RRMM who received ≥1 prior LOT, including lenalidomide. Here, we present a subgroup analysis in pts with FHR MM treated with 1 prior LOT. Methods: Pts treated with ≥1 prior LOT were randomized (1:1) to BVd or DVd in D7 and BPd or PVd in D8. The primary endpoint of both trials was independent review committee–assessed PFS. Key secondary endpoints for both trials were OS, MRD, and DOR. In the D7 and D8 trials, FHR was defined as RRMM that progressed ≤18 mo after the start of ASCT or start of first-line therapy. Descriptive statistics were used for response rates, MRD negativity (10−5) rates, and adverse events (AEs). Hazard ratios (HRs) for PFS, OS, and DOR were estimated with the Cox model. The Kaplan-Meier method estimated median survival times. Results: Baseline disease characteristics were generally balanced between treatment arms in pts with 1 prior LOT, regardless of FHR status. In D7, 125 pts per arm who received 1 prior LOT were treated with BVd or DVd, with 43 pts in each arm having FHR MM. In D8, 82 and 77 pts who received 1 prior LOT were treated with BPd and PVd, respectively, with 28 (BPd) and 31 pts (PVd) having FHR MM. In D7, median follow-up was 28.2 mo for pts who received 1 prior LOT and 39.4 mo for pts with FHR MM. In D8, median follow-up was 21.8 mo for all pts. In D7, median PFS was longer in the BVd vs DVd arm, both in pts with 1 prior LOT (36.6 mo vs 19.1 mo; HR, 0.52; 95% CI, 0.36-0.76), and in those with FHR MM (28.4 mo vs 13.4 mo; HR, 0.65; 95% CI, 0.37-1.14). Similarly, in D8, median PFS favored the BPd vs PVd arm, both in pts with 1 prior LOT (not reached [NR] vs 18.5 mo; HR, 0.50; 95% CI, 0.30-0.85) and in those with FHR MM (NR vs 14.8 mo; HR, 0.66; 95% CI, 0.28-1.54). In pts treated with 1 prior LOT in D7, ORR was similar between BVd and DVd arms (83% vs 82%), with greater depth of response in the BVd arm (≥ CR: 39% vs 24%). In pts treated with 1 prior LOT in D7, ≥ CR MRD negativity rates were 28% (35/125) with BVd vs 14% (18/125) with DVd. In D7 pts with FHR MM, both ORR (86% vs 74%) and depth of response (≥ CR: 33% vs 21%) were higher with BVd vs DVd, respectively. In D7 pts with FHR MM, ≥ CR MRD negativity rates were 21% (9/43) with BVd vs 9% (4/43) with DVd. In pts treated with 1 prior LOT in D8, ORR was higher with PVd (88%) vs BPd (79%); however, response was deeper with BPd (≥ CR: 46% vs 23%). In pts treated with 1 prior LOT in D8, ≥ CR MRD negativity rates were 33% (27/82) with BPd vs 5% (4/77) with PVd. In D8 pts with FHR MM, ORR was comparable between pts in the BPd and PVd arms (82% vs 87%, respectively), with greater depth of response seen with BPd (≥ CR: 50% vs 23%). In pts with FHR MM in D8, ≥ CR MRD negativity rates were higher with BPd (36% [10/28]) than with PVd (7% [2/31]). In both the D7 and D8 trials, mOS was NR in pts with 1 prior LOT, regardless of FHR status. Among D7 pts with FHR MM, 70% in the BVd arm and 58% in the DVd arm were alive. Among pts with FHR MM in D8, 79% in the BPd arm vs 77% in the PVd arm were alive. In D7 pts treated with 1 prior LOT and FHR MM, grade 3/4 treatment-related AEs (TRAEs) related to any study treatment occurred in 91% with BVd and 60% with DVd. In D8 pts treated with 1 prior LOT and FHR MM, grade 3/4 TRAEs related to any study treatment occurred in 78% with BPd and 71% with PVd. Conclusions: In both D7 and D8, BVd and BPd were associated with extended PFS vs standard-of-care (SOC) regimens DVd and PVd, respectively, in patients with FHR MM. Deeper responses with higher rates of ≥ CR MRD negativity were also observed vs SOC regimens in both studies. mOS was NR in both trials at the time of this analysis.Funding:GSK (study numbers: 207503; 207499). Drug linker technology licensed from Seagen Inc; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa