Belantamab mafodotin for the treatment of multiple myeloma

Advances in frontline multiple myeloma (MM) treatment, through combinatorial regimens with diverse mechanisms of action, have created a need for alternative agents at relapse. BCMA-targeting CAR-T therapies have already demonstrated superiority over conventional options. Belantamab mafodotin, a first-in-class BCMA-directed antibody - drug conjugate (ADC), has shown significant benefit in combination with proteasome inhibitors or immunomodulators, as an accessible alternative to CAR-T therapy.

Belantamab mafodotin-based regimens were approved for the treatment of MM from second line of therapy in UK (April 2025) and EU (July 2025) and is under extended review by the FDA after concerns raised regarding its safety profile. This review discusses its mechanism of action, along with efficacy and safety data, to evaluate its role in the evolving MM treatment landscape.

Belantamab mafodotin offers a distinct therapeutic profile: off-the-shelf availability compared to CAR-Ts, lower infection risk than T-cell engagers, and a mechanism of action distinct from both T-cell - redirecting and standard therapies. Ocular keratopathy is a class-specific adverse event that is manageable with appropriate measures. Its relatively low incidence of life-threatening infections supports its use, particularly in frail patients. Ongoing trials suggest a feasible integration into frontline regimens to further improve clinical outcomes.