On October 23, 2025, the U.S. Food and Drug Administration (FDA) approved belantamab mafodotin-blmf (Blenrep), a B-cell maturation antigen (BCMA)–directed antibody and microtubule inhibitor conjugate, in combination with bortezomib and dexamethasone for the treatment of adults with relapsed or refractory multiple myeloma who have received at least two prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.
DREAMM-7
Efficacy was evaluated in DREAMM-7 (ClinicalTrials.gov identifier NCT04246047), an open-label, multicenter trial in adults with relapsed or refractory multiple myeloma who had received at least one line of prior therapy. The trial excluded patients who were refractory or intolerant to daratumumab or bortezomib, had received prior BCMA-directed therapy, and had existing corneal disease (except for mild punctate keratopathy).
Patients were randomly assigned 1:1 to receive either belantamab mafodotin, bortezomib, and dexamethasone (BVd) or daratumumab, bortezomib, and dexamethasone (DVd). The efficacy population included 217 patients (108 and 109 in respective arms) who had received at least two prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.
Efficacy was established based on progression-free survival and overall survival. The median progression-free survival was 31.3 months (95% confidence interval [CI] = 23.5 months to not reached) in the BVd arm and 10.4 months (95% CI = 7–13.4 months) in the DVd arm (hazard ratio [HR] = 0.31; 95% CI = 0.21–0.47). The median overall survival was not reached and 35.7 months (95% CI = 21.1 months to not reached) in respective arms (HR = 0.49; 95% CI = 0.32–0.76).
Warnings and REMS
Prescribing information includes a boxed warning for the risk of ocular toxicity, including corneal epithelium changes resulting in vision deterioration. Among those receiving belantamab mafodotin in DREAMM-7, ocular toxicity occurred in 92% of patients, including grade 3 or 4 events in 77%, with 83% requiring dosage modification because of ocular toxicity.
Because of the risk of ocular toxicity, belantamab mafodotin is available only through a Risk Evaluation and Mitigation Strategy (REMS), called the BLENREP REMS. Other warnings and precautions include thrombocytopenia and embryofetal toxicity.
Recommended Dosage
The recommended dosage for belantamab mafodotin is 2.5 mg/kg once every 3 weeks in combination with bortezomib and dexamethasone for the first eight cycles, followed by belantamab mafodotin at 2.5 mg/kg once every 3 weeks as a single agent until disease progression or unacceptable toxicity. Prescribing information contains dosing instructions of the drugs administered in combination with belantamab mafodotin.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
Belantamab mafodotin has received Orphan Drug designation.
