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

Abstract

BackgroundPatients 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.MethodsDREAMM‐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).ResultsThis 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.ConclusionsThis 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.

Belantamab mafodotin in triple‐refractory multiple myeloma patients: A retro‐prospective observational study in Italy

“…This was probably due to the lower number of prior LOTs of patients enrolled in our series (median: five lines vs. seven lines in DREAMM‐2). Median OS was similar in both studies: 12 months in our series versus 15.3 months reported in the final analysis of DREAMM‐2 study [ 3 ]. Several real‐world studies with belantamab mafodotin monotherapy in RRMM have been recently published, confirming data from DREAMM‐2 trial.…”

“…Belantamab mafodotin is the first‐in‐class antibody‐drug conjugates (ADC) targeting B‐cell maturation antigen (BCMA) approved for relapsed/refractory multiple myeloma (RRMM) who received at least four prior LOTs including a PI, an IMiD, and an anti‐CD38 mAb. Approval was based on the results of the phase II, open‐label, two‐arm, multicenter DREAMM‐2 trial [ 3 ]—primary endpoint was overall response rate (ORR). RRMM patients with a median of six prior LOTs were allocated to receive belantamab mafodotin 2.5 or 3.4 mg/kg every 3 weeks until disease progression or unacceptable toxicity.…”

Novel Immunotherapies and Combinations: The Future Landscape of Multiple Myeloma Treatment

“…In the pivotal DREAMM-2 trial, grade 1-2 keratopathy occurred in 43% and 54% of patients receiving belamaf 2.5 mg/kg and 3.4 mg/kg, respectively, whereas grade 3 keratopathy was seen in 27% and 20% of the first and latter cohorts, with only 1% of patients developing grade 4 keratopathy in the 3.4 mg/kg group [64]. BCVA reduced to 20/50 or worse was documented in 48% and 49% of the 2.5 mg/kg and 3.4 mg/kg cohorts, respectively, whereas blurred vision occurred in 25% and 36% and dry eye in 18% and 25%, respectively [65]. Ocular events resolved in 36% of patients receiving 2.5 mg/kg and in 28% of those treated with 3.4 mg/kg, with a median time to resolution of 71 days and 96 days, respectively.…”

Incorporating Immunotherapeutic Strategies in the Management of Relapsed/Refractory Multiple Myeloma

“…Kumar briefly touched on the one BCMA-targeted antibody-drug conjugate, belantamab mafodotin, approved for R/R myeloma, based on the results of DREAMM-2. 6 However, the drug was withdrawn when the subsequent phase III DREAMM-3 trial failed to show improved outcomes over pomalidomide 1 dexamethasone. 7 "Other phase III trials are ongoing, so we will probably be hearing more about this drug in the future," he added.…”