Final analysis of the phase I DREAMM-9 trial: BVRd for TI NDMM

Final results from the phase I DREAMM-9 trial (NCT04091126), evaluating belantamab mafodotin (belamaf) + bortezomib + lenalidomide + dexamethasone (BVRd) in adults with transplant-ineligible (TI) newly diagnosed multiple myeloma (NDMM) (N = 118; safety population, n = 115), were presented by Enrique M. Ocio at the European Hematology Association (EHA) 2026 Congress, June 11–14, 2026, Stockholm, SE. The study aimed to identify the optimal belamaf dose and schedule among eight induction/maintenance schedules: 1.0, 1.4, or 1.9 mg/kg every 3 weeks (Q3W) during induction followed by every 4 weeks (Q4W) during maintenance; 1.4 or 1.9 mg/kg every 6 weeks (Q6W) followed by every 8 weeks (Q8W); first-dose step-down regimens of 1.9 mg/kg followed by 1.4 mg/kg every 9 weeks (Q9W), or 1.4 mg/kg followed by 1.0 mg/kg Q9W, during induction, with every 12 weeks (Q12W) during maintenance; and 1.0 mg/kg Q12W throughout. The primary endpoint was safety, including dose-limiting toxicities (DLTs) and adverse events (AEs). 

Key data: Grade ≥3 ocular AEs occurred in 74%, 88%, and 35% of patients with the Q3/4W, Q6/8W, and Q9/12W or Q12/12W schedules, respectively; first-event resolution rates were 97%, 86%, and 100%, respectively. Belamaf discontinuation due to Grade ≥3 ocular events was low (3%), occurring only in the Q3/4W cohorts. The overall response rates (ORRs) were 90%, 96%, and 85% with the Q3/4W, Q6/8W, and Q9/12W or Q12/12W schedules, respectively; complete response or better (≥CR) rates were 68%, 88%, and 59%, respectively. In the Q6/8W cohorts, belamaf induction at 1.9 mg/kg vs 1.4 mg/kg showed higher rates of ≥CR (92% vs 83%) and MRD-negativity (67% vs 42%). Relative dose intensity (RDI) was highest and most stable with extended dosing schedules, while vision-related functioning (VRF) was generally maintained with extended dosing intervals.

Key learning: DREAMM-9 data support a BVRd induction/maintenance dosing strategy with higher belamaf dose intensity during induction to deepen responses, followed by extended maintenance intervals to improve tolerability. These findings support the 1.9 mg/kg Q8W for 24 weeks followed by Q12W dosing schedules being used in the ongoing phase III DREAMM-10 and PrE1005 trials.