Single‐agent belantamab mafodotin in patients with relapsed/refractory multiple myeloma: Final analysis of the DREAMM‐2 trial.

Background: Patients with relapsed/refractory multiple myeloma (RRMM) have a high unmet treatment need. Belantamab mafodotin (belamaf), a first‐in‐class, B‐cell maturation antigen‐binding antibody‐drug conjugate, eliminates myeloma cells through direct cell killing and an anti‐myeloma immune response. Methods: DREAMM‐2 (NCT03525678) was a phase 2, two‐arm, open‐label trial in patients with heavily pretreated RRMM who had three or more prior therapies, were refractory to an immunomodulatory agent and a proteasome inhibitor, and refractory or intolerant to an anti‐CD38 monoclonal antibody. Belamaf was given at 2.5 or 3.4 mg/kg every 3 weeks. The primary end point was overall response rate (ORR); secondary end points included progression‐free survival (PFS), overall survival (OS), safety, ocular symptoms, and health‐related quality of life (HRQOL). Results: This final analysis (cutoff date, March 31, 2022), N = 223, with median follow‐up of 12.5 and 13.8 months, demonstrated an ORR of 32% and 35%, median PFS of 2.8 and 3.9 months, and median OS of 15.3 and 14.0 months in the 2.5 mg/kg and 3.4 mg/kg cohorts, respectively. Median duration of response was 12.5 and 6.2 months. No new safety signals were observed; the most common Grade 3 and 4 adverse events were keratopathy (29% vs. 25%), thrombocytopenia (22% vs. 29%), and anemia (21% vs. 28%). HRQOL outcomes suggest that overall global health status/quality of life, physical and role functioning, and overall disease symptoms were maintained or improved during treatment. Conclusions: This final analysis of DREAMM‐2 confirms that in patients with triple‐class refractory RRMM, single‐agent belamaf results in durable and clinically meaningful responses with a manageable safety profile. Although much progress has been made in the treatment landscape for patients with relapsed/refractory multiple myeloma (RRMM), outcomes remain poor once the disease becomes refractory to multiple therapies. The results of the final analysis of the DREAMM‐2 trial further establish that treatment with single‐agent belamaf results in clinically meaningful responses with a manageable safety profile in patients with RRMM who had received at least three previous lines of therapy. [ABSTRACT FROM AUTHOR]