Efficacy and Safety of Belantamab Mafodotin with Bortezomib Plus Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: the DREAMM-6 Arm B Trial.

Abstract

The Phase 1/2 DREAMM-6 Arm B study (NCT03544281) explored belantamab mafodotin combined with bortezomib/dexamethasone (BVd) in relapsed/ refractory multiple myeloma (RRMM). Adults with RRMM were enrolled sequentially in two belantamab mafodotin (intravenous) dose-escalation (DE) cohorts (2.5 then 3.4 mg/kg every 3 weeks [Q3W]). Additional patients enrolled sequentially to eight dose-expansion cohorts: 1.9, 2.5, or 3.4 mg/kg Q3W; 2.5 or 3.4 mg/kg Q3W split dose (Days 1 and 8); 1.9 or 2.5 mg/kg Q6W; or 2.5 mg/kg in cycle 1 stepped down to 1.9 mg/kg Q6W thereafter. Patients received bortezomib twice weekly and dexamethasone four times weekly. Endpoints were dose-limiting toxicities (DLT; DE), adverse events (AEs), serious AEs (SAEs; DE and expansion), overall response rate (ORR; expansion), and pharmacokinetics. 107 patients (median 4 prior lines of therapy) received BVd (n=12-18/ cohort). Median follow-up was 15.2-25.4 months. No DLTs occurred during DE. The most common Grade 3/4 AE was keratopathy (53%). Protocol-defined ocular events (change in best corrected visual acuity and/or corneal examination findings) were reported in 93% of patients (Grade 3/4: 77%). Twenty-eight (26%) patients experienced any study treatment-related SAEs; 3 of 7 fatal SAEs had a treatment-related primary cause. ORR was 70% (95% CI: 60.5, 78.6). Higher initial exposures had higher probabilities of response and ocular events; lower exposures resulted in fewer deep responses, with small differences in ocular events. BVd demonstrated manageable safety and clinical activity across all dosing cohorts in heavily pretreated RRMM, supporting the 2.5 mg/kg Q3W dose.