Belantamab mafodotin (BCMA ADC) + VRd in DREAMM-9 delivers ≥83% ORR in transplant-ineligible NDMM, with dose-intensity–driven depth vs ocular toxicity tradeoff

Belantamab mafodotin (belamaf) is an anti-BCMA antibody–drug conjugate combined here with bortezomib/lenalidomide/dexamethasone (VRd) as BVRd in the DREAMM-9 Phase 1 dose/schedule optimization study in transplant-ineligible newly diagnosed multiple myeloma (n=118; NCT04091126; data cut June 2, 2025; median follow-up 15.9–47.1 months). ORR was ≥83% across 8 belamaf dosing cohorts, while higher induction dose intensity delivered deeper responses (pooled SHORT+STRETCH: CR+/MRD[-] 75%/55% vs pooled Q9/12W+Q12W: 59%/43%) but at the cost of more ocular toxicity (Gr≥2 ophthalmic exam findings 90% vs 69%; Gr3/4 79% vs 35%); Gr≥2 events resolved before end of treatment in 83–100%, and discontinuations for Gr≥3 ocular events occurred only in SHORT cohorts (1 patient each). Efficacy looks directionally in-family with current frontline TI NDMM quadruplets built on anti-CD38 + VRd (e.g., D-VRd in CEPHEUS improved depth/MRD and PFS vs VRd), but DREAMM-9 is non-comparative and the ocular AE burden is a differentiator that anti-CD38–based regimens largely don’t carry.