Belantamab mafodotin, a BCMA-directed antibody-drug conjugate for multiple myeloma

Belantamab mafodotin-blmf (bela-maf) is a first-in-class antibody-drug conjugate (ADC) that targets B-cell maturation antigen (BCMA) for the treatment of multiple myeloma. Its unique structure allows it to induce plasma cell apoptosis through microtubule inhibition, antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP). While bela-maf failed to show efficacy as monotherapy for relapsed/refractory myeloma in its initial phase 3 trial, it subsequently showed significant improvement in progression-free survival in combination with either bortezomib/dexamethasone (BVd, DREAMM-7) or pomalidomide/dexamethasone (BPd, DREAMM-8) resulting in updated regulatory approval. Bela-maf is an "off-the-shelf" BCMA-directed therapy with decreased risk of severe infections compared to other T cell redirection strategies, but it results in high incidence of ocular toxicity including keratopathy, blurred vision, and dry eye due to target-independent uptake of the monomethyl auristatin F (MMAF) payload in the corneal epithelium. Bela-maf-induced ocular toxicity requires close ophthalmology monitoring and may be partially mitigated by reducing the dose or frequency of bela-maf, and further data are needed to optimize dosing strategies. Herein, we review the pharmacology, clinical efficacy, and unique safety precautions related to belantamab mafodotin, as well as highlight ongoing studies of its use in earlier lines of therapy and in combination with other anti-myeloma agents.