A Phase 1, open-label study, DREAMM-11, investigated the tolerability, safety, efficacy, and pharmacokinetics of belantamab mafodotin in Japanese patients with relapsed/refractory multiple myeloma (RRMM). Part 2 of the study focused on combination therapies with either bortezomib plus dexamethasone or pomalidomide plus dexamethasone. The results suggest promising clinical activity and manageable safety profiles, warranting further investigation in this patient population.
The study addresses the unmet need for effective treatments in RRMM, where patients often relapse or become refractory to available therapies. Belantamab mafodotin, an antibody-drug conjugate (ADC) targeting B-cell maturation antigen (BCMA), has shown promise in previous trials. This study aimed to evaluate its use in combination with standard-of-care regimens in a Japanese population.
Study Design and Methods
DREAMM-11 Part 2 (NCT03828292) enrolled Japanese patients with RRMM who had received at least one prior line of therapy. Arm A received belantamab mafodotin (2.5 mg/kg every 3 weeks) plus bortezomib (1.3 mg/m2 on Days 1, 4, 8, and 11) and dexamethasone (20 mg on Days 1, 2, 4, 5, 8, 9, 11, and 12). Arm B received belantamab mafodotin (2.5 mg/kg on Day 1 of the first 28-day cycle, then 1.9 mg/kg on Day 1 of subsequent cycles) plus pomalidomide (4 mg daily on Days 1-21) and dexamethasone (40 mg on Days 1, 8, 15, and 22). The primary endpoint was tolerability, assessed by dose-limiting toxicities (DLTs) and adverse events (AEs). Secondary endpoints included overall response rate (ORR) per International Myeloma Working Group criteria and pharmacokinetics (PK).
Key Findings
In Arm A, no DLTs were reported. In Arm B, one DLT of non-serious Grade 3 liver injury was observed. All patients in both arms experienced at least one AE related to belantamab mafodotin. Common Grade ≥3 AEs included thrombocytopenia (100% in Arm A, 50% in Arm B) and lymphopenia (67% in Arm A). Corneal events, managed with dose adjustments, were reported in all patients. The ORR was 100% in Arm A and 50% in Arm B. All patients in Arm A achieved a VGPR. PK parameters were consistent with those observed in Western populations.
Clinical Implications
The high ORR observed in the belantamab mafodotin, bortezomib, and dexamethasone arm aligns with findings from the DREAMM-7 trial, which demonstrated improved progression-free survival compared to daratumumab, bortezomib, and dexamethasone. The study supports the inclusion of Japanese patients in global Phase 3 trials of belantamab mafodotin combinations. While the small sample size is a limitation, the results provide valuable insights into the tolerability and efficacy of these combinations in a previously underrepresented population.
The DREAMM-11 study provides evidence supporting the use of belantamab mafodotin in combination with bortezomib and dexamethasone or pomalidomide and dexamethasone for Japanese patients with RRMM. The manageable safety profile and promising clinical activity observed warrant further investigation in larger, global trials.
