DREAMM-9 final analysis: Belantamab mafodotin (belamaf), bortezomib, lenalidomide, and dexamethasone (BVRd) for transplant-ineligible (TI) newly diagnosed multiple myeloma (NDMM).

Abstract

7503 Background: DREAMM-9 (NCT04091126) was a phase 1 dose and schedule evaluation study of BVRd in adults with TI NDMM. Methods: Patients (pts) received BVRd in 1 of 8 belamaf dosing cohorts at an induction/maintenance schedule of Q3/4W (SHORT: 1.9, 1.4, 1.0 mg/kg), Q6/8W (STRETCH: 1.9, 1.4 mg/kg), Q9/12W (step-down [S/D]: 1.9 for 1 dose then 1.4 mg/kg; 1.4 for 1 dose then 1.0 mg/kg), or Q12W (1.0 mg/kg). The primary endpoint was safety. Responses, minimal residual disease negativity (MRD[-]) in complete response or better (CR+), and pt-reported outcomes (PROs) were assessed. Median dose intensities (mDIs) were calculated as mg/kg/21 days in induction and mg/kg/28 days in maintenance. Results: As of June 2, 2025, 118 pts were enrolled (intention-to-treat population). Median duration of follow-up was 15.9–47.1 months. Induction mDI generally decreased as planned dosing intervals increased and was lowest in S/D Q9/12W or Q12W cohorts. Maintenance mDI was similar across cohorts due to dose modifications. Overall response rates were ≥83% across cohorts. Cohorts with higher induction mDI had the deepest responses (CR+/MRD[-] 75/55% for pooled SHORT+STRETCH and 59/43% for pooled Q9/12W+Q12W). Grade (Gr) ≥2 ophthalmic exam findings (OEFs; best-corrected visual acuity changes/slit lamp findings [Keratopathy and Visual Acuity scale]) were 90% for pooled SHORT+STRETCH/69% for pooled Q9/12W+Q12W, while Gr 3/4 OEF rates were higher with higher induction mDI (79%/35%). Most cohorts (5/8) had no belamaf discontinuations due to Gr ≥3 OEFs, which occurred only in SHORT cohorts (n = 1 each). First Gr ≥2 OEFs resolved prior to end of treatment in 83–100% across cohorts. The long-interval group (Q9/12W and Q12W dosing schedules) remained largely below the vision-related function (VRF) deterioration threshold (12.5 points per Ocular Surface Disease Index) across most timepoints, suggesting a favorable VRF profile vs the SHORT interval group. Conclusions: BVRd had high response rates across all cohorts (≥83%), highlighting the promising efficacy of the regimen. Regimens with higher belamaf induction mDI had the deepest responses, while those with lower induction mDI had milder OEFs. Belamaf dosing with a higher induction DI is optimal to achieve deeper responses, and a lower maintenance DI (i.e., using longer schedules) improves tolerability, PROs, and maintains responses. Clinical trial information: NCT04091126 .