Phase 2 DREAMM-15: belantamab mafodotin BCMA-targeting MMAF ADC in RRMM combinations

GlaxoSmithKline’s DREAMM-15 is a Phase 2, multicenter, open-label, non-randomized study testing extended-interval dosing of belantamab mafodotin (Blenrep)—a BCMA-directed antibody–drug conjugate delivering MMAF, a microtubule inhibitor—in relapsed/refractory multiple myeloma after 1–2 prior lines (2nd–3rd line). Participants receive belantamab in three combination arms with standard backbones: BPd (with pomalidomide, a cereblon-modulating IMiD, plus dexamethasone), BVd (with bortezomib, a 26S proteasome inhibitor, plus dexamethasone), or BKd (with carfilzomib, an irreversible proteasome inhibitor, plus dexamethasone). The scientific angle is dose/schedule optimization: the trial asks whether giving belantamab less often can preserve efficacy while reducing ocular toxicity (keratopathy/vision changes) that has limited broader use. For many patients in this setting, today’s care is sequential triplets built around a proteasome inhibitor or IMiD plus steroid, increasingly incorporating anti-CD38 antibodies and later-line cellular therapy or bispecifics when feasible; this study explores whether a BCMA ADC can be more tolerable when layered onto common 2nd–3rd line regimens.