DREAMM-2: Single-Agent Belantamab Mafodotin (Belamaf) in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) – 1-Year Outcomes By Prior Therapies

Introduction: Most patients with multiple myeloma, including those previously exposed to anti-CD38 monoclonal antibodies (mAbs), progress after successive lines of treatment. With each subsequent regimen, the response to treatment and disease-free intervals decrease; therefore, new treatments are urgently needed for RRMM. Patients refractory to anti-CD38 mAbs have a poor prognosis and few treatment options. The pivotal DREAMM-2 study (NCT03525678) demonstrated that belamaf (GSK2857916; B-cell maturation antigen–targeting antibody-drug conjugate) had deep and durable activity and a manageable safety profile with up to 13 months of follow-up in patients with heavily pretreated RRMM (Lonial et al. ASCO 2020 Poster 436). Here we report on the efficacy, safety, and tolerability of single-agent belamaf after 13 months of follow-up in a subgroup analysis of patients with varying numbers of prior therapies.

Methods: Patients with RRMM after ≥3 prior therapies, refractory to an immunomodulatory agent and a proteasome inhibitor, and refractory and/or intolerant to an anti-CD38 mAb who provided informed consent received treatment with single-agent belamaf (2.5 or 3.4 mg/kg intravenously every 3 weeks [Q3W]). The primary endpoint was overall response rate (ORR; ≥partial response per independent review committee). Other key endpoints included duration of response (DoR), progression-free survival (PFS), overall survival, and safety. This post hoc analysis examined patients treated with the 2.5-mg/kg Q3W dose of single-agent belamaf (selected as the recommended dose for future clinical development) categorized into two groups: 3–6 and ≥7 prior therapies.

Results: In DREAMM-2, 97 patients were enrolled in the 2.5-mg/kg cohort with a median of 7 (3–21) prior therapies and a median follow-up of 12.4 months at January 31, 2020. The median (range) age of patients in the 3–6 and ≥7 prior therapies groups was 62 (39–85) and 67 (45–85) years, respectively. By International Staging System grade, the corresponding proportions of patients with Stage II or III disease were 76% and 78%, respectively. High-risk cytogenetics, defined as t(4;14), t(14;16), and 17p13del, were present in 26% of patients with 3–6 and 28% of those with ≥7 prior therapies.

Forty-seven (48%) patients had 3–6 prior therapies, and 50 (52%) had ≥7 prior therapies. The ORR was 34% and 30% in patients with 3–6 and ≥7 prior therapies. Across all patients, 17% with 3–6 prior therapies had ≥very good partial responses (VGPR; 50% [8/16] responders) and 20% of those with ≥7 prior therapies had ≥VGPR (67% [10/15] responders). The DoR was 11.0 months and 13.1 months, and the median PFS was 2.9 and 2.2 months, in patients with 3–6 and ≥7 prior therapiesrespectively. The most common Grade 3/4 adverse events (AEs; >10% in the 3–6 or ≥7 prior therapies groups) were keratopathy (microcyst-like epithelial changes observed on eye examination with or without symptoms; 3–6: 33%; ≥7: 27%), thrombocytopenia (3–6: 17%; ≥7: 20%), anemia (3–6: 11%; ≥7: 31%), and decreased lymphocyte count (3–6: 11%; ≥7: 14%). In the 3–6 or ≥7 prior therapies groups, AEs were managed with dose delays (3–6: 59%; ≥7: 49%) and reductions (3–6: 37%; ≥7: 33%); discontinuations due to treatment-related AEs were uncommon (3–6: 7%; ≥7: 8%).

Conclusions: Single-agent belamaf 2.5 mg/kg Q3W was well tolerated and efficacious in the treatment of patients with RRMM, with comparable ORR, DoR, and PFS, and a manageable safety profile irrespective of the number of prior lines of therapy.

Funding: GSK (Study 205678); drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa.