Background
Phase 3, open-label, randomized controlled trial (DREAMM-8). N=302 patients with RRMM who received 1–3 prior lines including a lenalidomide-containing regimen; both lenalidomide-exposed and lenalidomide-refractory patients enrolled. Prior anti-BCMA therapy was excluded. Randomized 1:1.
Interventions and follow up
Arm A: Belantamab mafodotin 2.5 mg/kg IV cycle 1 then 1.9 mg/kg q4wk + pomalidomide 4 mg PO days 1–21 q28d + dexamethasone 40 mg weekly (BPd)
Arm B: Bortezomib 1.3 mg/m² SC days 1, 4, 8, 11 (cycles 1–8) then days 1, 8 (cycles ≥9) + pomalidomide 4 mg days 1–21 q28d + dexamethasone 40 mg weekly (PVd)
Primary endpoint: Progression-free survival (PFS)
mFollow up: 21.8 months
Arm B: Bortezomib 1.3 mg/m² SC days 1, 4, 8, 11 (cycles 1–8) then days 1, 8 (cycles ≥9) + pomalidomide 4 mg days 1–21 q28d + dexamethasone 40 mg weekly (PVd)
Primary endpoint: Progression-free survival (PFS)
mFollow up: 21.8 months
Results
mPFS: Not reached vs 12.7 months (BPd vs PVd), HR 0.52 (95% CI 0.37–0.73), P<.001
12-mo PFS rate: 71% vs 51%
ORR: 77% vs 72%
≥VGPR: 66% vs 50%
≥CR: 40% vs 16%
12-mo PFS rate: 71% vs 51%
ORR: 77% vs 72%
≥VGPR: 66% vs 50%
≥CR: 40% vs 16%
Adverse events
Ocular (BPd): Keratopathy any grade 90%, grade ≥3 47%; dose interruptions required in the majority of belantamab-treated patients
Hematologic (grade ≥3, BPd): Thrombocytopenia 24%, neutropenia 22%
Neuropathy: Peripheral neuropathy grade ≥3 2% (BPd) vs 18% (PVd); discontinuation due to AEs 20% vs 15%
Hematologic (grade ≥3, BPd): Thrombocytopenia 24%, neutropenia 22%
Neuropathy: Peripheral neuropathy grade ≥3 2% (BPd) vs 18% (PVd); discontinuation due to AEs 20% vs 15%
Conclusions
BPd significantly improved PFS over PVd in RRMM patients with prior lenalidomide exposure, with deeper responses and avoidance of bortezomib-related neuropathy. This established BPd as an approved option in lenalidomide-exposed RRMM.
Key Limitations
Keratopathy management requires mandatory ophthalmology monitoring with frequent dose interruptions and modifications, significantly limiting real-world adoption. The PVd comparator is not universally preferred; anti-CD38 + pomalidomide-based triplets (IsaPd, DaraPd) are commonly used and offer comparable efficacy without ocular toxicity. OS data remain immature. Complex dose-modification algorithms may impair real-world efficacy relative to trial conditions.
Clinical Context
FDA approved BPd in 2025 for RRMM after ≥1 prior therapy including lenalidomide. Competing pomalidomide-based triplets with anti-CD38 antibodies (IsaPd from ICARIA-MM; DaraPd from APOLLO) offer comparable or greater efficacy without ocular toxicity and are preferred at many centers. A REMS program for ocular monitoring is required for all belantamab prescribers. ESMO-MCBS reflects substantial PFS benefit.