Belantamab Mafodotin for Patients With Multiple Myeloma: Clinical Development and Practical Strategies for Dose Optimization and Toxicity Management.

Belantamab mafodotin (belamaf) is an antibody-drug conjugate targeting B-cell maturation antigen on plasma cells. The phase III DREAMM-7 and DREAMM-8 trials, in which belamaf was combined with bortezomib-dexamethasone or pomalidomide-dexamethasone, respectively, showed significantly higher overall response and measurable residual disease negativity rates for belamaf-combinations as compared to standard-of-care triplets, as well as improved longitudinal outcomes. Collectively, the results of DREAMM-7 and DREAMM-8 have established these regimens as a treatment option for patients with relapsed or refractory multiple myeloma, leading to regulatory approval of belamaf in combination with bortezomib by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), and in combination with pomalidomide by the EMA. Belamaf is associated with a distinctive spectrum of eye-related adverse events (AEs), largely attributable to the off-target effect of its cytotoxic payload, the monomethyl auristatin F (MMAF). Despite their frequent occurrence, eye-ocular AEs have been shown to be reversible, and have rarely led to belamaf discontinuation. Multiple dosing strategies and schedules of the drug have been explored in phase I/II and III trials in an attempt to optimize its efficacy while limiting ocular toxicity. In this review, we summarize the current literature regarding efficacy and safety of belamaf, with a focus on ocular toxicity. We discuss current recommendations for eye-related AE assessment and emerging strategies for dose optimization and toxicity management, aiming to maximize therapeutic benefit while minimizing ocular toxicity.