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

purposeThe phase I/II DREAMM-6 arm B study (NCT03544281) explored belantamab mafodotin combined with bortezomib/dexamethasone (BVd) in relapsed/refractory multiple myeloma (RRMM). PATIENTS AND

methodsAdults with RRMM were enrolled sequentially in two belantamab mafodotin (intravenous) dose-escalation (DE) cohorts (2.5 then 3.4 mg/kg every 3 weeks). Additional patients enrolled sequentially to eight dose-expansion cohorts: 1.9, 2.5, or 3.4 mg/kg every 3 weeks; 2.5 or 3.4 mg/kg every 3 weeks split dose (days 1 and 8); 1.9 or 2.5 mg/kg every 6 weeks; or 2.5 mg/kg in cycle 1 stepped down to 1.9 mg/kg every 6 weeks thereafter. Patients received bortezomib twice weekly and dexamethasone four times weekly. Endpoints were dose-limiting toxicities (DLT; DE), adverse events (AE), serious AEs (SAE; DE and expansion), overall response rate (ORR; expansion), and pharmacokinetics.

resultsOne hundred seven patients (median 4 prior lines of therapy) received BVd (n = 12-18/cohort). The median follow-up was 15.2 to 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. The ORR was 70% (95% confidence interval, 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.

conclusionsBVd demonstrated manageable safety and clinical activity across all dosing cohorts in heavily pretreated RRMM, supporting the 2.5 mg/kg every 3 weeks dose.