Purpose: The Phase 1/2 DREAMM-6 Arm B study (NCT03544281) explored belantamab mafodotin combined with bortezomib/dexamethasone (BVd) in relapsed/ refractory multiple myeloma (RRMM).

Patients and methods: 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.

Results: 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.

Conclusion: BVd demonstrated manageable safety and clinical activity across all dosing cohorts in heavily pretreated RRMM, supporting the 2.5 mg/kg Q3W dose.