Belantamab Mafodotin, Bortezomib, and Dexamethasone Vs Daratumumab, Bortezomib, and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Overall Survival Analysis and Updated Efficacy Outcomes of the Phase 3 Dreamm-7 Trial

Patients with multiple myeloma (MM) are initially treated with triplet or quadruplet combination regimens that include proteasome inhibitors, immunomodulators, and anti-CD38 monoclonal antibodies. However, most patients with MM experience progression after initial treatment and need efficacious subsequent-line combinations that incorporate new drug classes. Multiple studies in this relapsed/refractory MM population have shown progression-free survival (PFS) benefit; however, it is important that this translates into overall survival (OS) benefit for patients, as OS considers both efficacy and safety. Currently, daratumumab-containing regimens are widely used in this setting because triplet daratumumab combinations have shown significant PFS and OS benefits compared with their respective doublet backbones without daratumumab. Belantamab mafodotin, a B-cell maturation antigen-targeting antibody-drug conjugate, has demonstrated single-agent sustained maintenance of deep and durable response with longer follow-up, owing to its multimodal mechanism of action that includes monomethyl auristatin F-induced cytotoxic cell death, antibody-dependent cellular cytotoxicity/phagocytosis, and immunogenic cell death. This has led to improvement in long-term clinical outcomes, including duration of response (DOR). Therefore, we anticipate that belantamab mafodotin in combination with standard-of-care therapies will show increasing OS benefit with longer follow-up. DREAMM-7 (NCT04246047) is a global, 1:1 randomized, open-label, phase 3, head-to-head trial comparing the efficacy and safety of 2 triplets-belantamab mafodotin, bortezomib, and dexamethasone (BVd) vs daratumumab, bortezomib, and dexamethasone (DVd)-in patients with progression of MM after ≥1 prior line of therapy. The primary endpoint was independent review committee-assessed PFS. Secondary endpoints included OS, DOR, minimal residual disease (MRD) negativity, and time from randomization to disease progression after subsequent antimyeloma therapy or death from any cause (PFS2) (Hungria et al. N Engl J Med 2024). In total, 494 patients were randomly assigned to receive BVd (n=243) or DVd (n=251). Baseline characteristics were balanced; overall, 51% of patients had received 1 previous line of therapy, 52% had exposure to lenalidomide, 34% had disease that was refractory to lenalidomide, and 28% had high-risk cytogenetic abnormalities. At a median follow-up of 28.2 months (range, 0.1-40.0 months), the primary endpoint was met, with a median PFS (95% CI) of 36.6 months (28.4 months-not reached [NR]) with BVd and 13.4 months (11.1-17.5 months) with DVd (hazard ratio [HR], 0.41; 95% CI, 0.31-0.53; P<.00001). BVd was associated with higher rates of complete response or better plus MRD negativity (25% vs 10%) and a more favorable restricted mean DOR (P<.001) than DVd. The median DOR (95% CI) was 35.6 months (30.5 months-NR) with BVd and 17.8 months (13.8-23.6 months) with DVd. Treatment benefits with BVd were also maintained after subsequent antimyeloma therapy, with an HR (95% CI) for median PFS2 of 0.56 (0.41-0.76). OS rates at 18 months with BVd vs DVd was 84% vs 73%, respectively. While median OS was NR in either arm at this first interim analysis, there was a strong trend in favor of BVd vs DVd, with an HR of 0.57 (95% CI, 0.40-0.80). Of note, in the CASTOR trial, median OS with DVd was 49.6 months in patients with a median of 2 prior lines of therapy. We will present the results from the second planned interim analysis of DREAMM-7, with an approximate 3.3 years of follow-up; this will provide further insight on the potential survival benefit with BVd and include updates on response depth, DOR, MRD-negativity rates, and PFS2. Overall, the DREAMM-7 head-to-head study of BVd vs DVd demonstrated statistically significant PFS benefit with BVd in patients with relapsed/refractory MM who have received ≥1 prior line of therapy. BVd also led to a deeper response and longer DOR than DVd. Since a strong and clinically meaningful early OS benefit with BVd was observed, updated practice-changing OS results are anticipated and will be presented at ASH 2024. Taken together, these results support BVd as a potential new standard of care in MM at first relapse or later. Funding: GSK (Study # 207503) Drug linker technology licensed from Seagen Inc.; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa.

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