Background
Phase 3, open-label, randomized controlled trial (DREAMM-7). N=494 patients with RRMM who had received ≥1 prior line including an immunomodulatory agent. Randomized 1:1. Belantamab mafodotin is an anti-BCMA ADC with a monomethyl auristatin F (MMAF) payload. Prior anti-BCMA therapy or prior daratumumab was excluded.
Interventions and follow up
Arm A: Belantamab mafodotin 2.5 mg/kg IV q3wk + bortezomib 1.3 mg/m² SC days 1, 4, 8, 11 (cycles 1–8) then days 1, 8 (cycles ≥9) + dexamethasone 20 mg (BVd)
Arm B: Daratumumab 16 mg/kg IV (q3wk cycles 1–3 → q4wk cycles 4–8 → q8wk cycles ≥9) + bortezomib (same schedule) + dexamethasone 20 mg (DVd)
Primary endpoint: Progression-free survival (PFS)
mFollow up: 28.2 months
Arm B: Daratumumab 16 mg/kg IV (q3wk cycles 1–3 → q4wk cycles 4–8 → q8wk cycles ≥9) + bortezomib (same schedule) + dexamethasone 20 mg (DVd)
Primary endpoint: Progression-free survival (PFS)
mFollow up: 28.2 months
Results
mPFS: 36.6 vs 13.4 months (BVd vs DVd), HR 0.41 (95% CI 0.31–0.53), P<.001
ORR: 77% vs 62%
≥VGPR: 57% vs 42%
≥CR: 34% vs 15%
mOS (interim): HR 0.57 (95% CI 0.40–0.80); formal OS testing not triggered at interim
ORR: 77% vs 62%
≥VGPR: 57% vs 42%
≥CR: 34% vs 15%
mOS (interim): HR 0.57 (95% CI 0.40–0.80); formal OS testing not triggered at interim
Adverse events
Ocular (BVd): Keratopathy any grade 89%, grade ≥3 35%; ophthalmology exam required before each dose with protocol-defined interruptions/reductions
Hematologic (grade ≥3, BVd): Thrombocytopenia 28%, neutropenia 25%; pneumonia grade ≥3 10%
Overall: Grade ≥3 events 92% (BVd) vs 83% (DVd); discontinuation due to AEs 19% vs 11%
Hematologic (grade ≥3, BVd): Thrombocytopenia 28%, neutropenia 25%; pneumonia grade ≥3 10%
Overall: Grade ≥3 events 92% (BVd) vs 83% (DVd); discontinuation due to AEs 19% vs 11%
Conclusions
BVd demonstrated a clinically meaningful PFS benefit over DVd in RRMM, with a median PFS of 36.6 months among the longest reported in a randomized RRMM trial. The trial supported FDA approval of belantamab mafodotin + bortezomib + dexamethasone for RRMM after ≥1 prior line including an IMiD.
Key Limitations
Keratopathy management requires ophthalmology co-management at every treatment cycle, posing substantial real-world feasibility challenges outside specialized centers. The DVd comparator was largely supplanted by more contemporary triplets at time of enrollment. Open-label design introduces bias in dose-modification decisions. Prior daratumumab was excluded, limiting applicability to anti-CD38–exposed populations. OS data immature at primary analysis.
Clinical Context
FDA approved BVd in 2025 for RRMM after ≥1 prior therapy, representing belantamab's return after the 2022 voluntary withdrawal of its single-agent accelerated approval following the DREAMM-3 failure. A REMS program for ocular monitoring remains in effect. DREAMM-8 provides a companion BPd regimen in lenalidomide-exposed RRMM. ESMO-MCBS reflects substantial PFS benefit.