Belantamab Mafodotin in Multiple Myeloma: A Comprehensive Review of a First-in-Class BCMA-Targeted Antibody-Drug Conjugate

Executive Summary and Drug Profile

Belantamab mafodotin represents a significant therapeutic innovation in the management of multiple myeloma (MM), standing as the first-in-class antibody-drug conjugate (ADC) designed to target B-cell maturation antigen (BCMA).[1] Its development and clinical journey have been characterized by both remarkable successes and notable setbacks, providing a compelling case study in modern oncology drug development. Initially granted accelerated and conditional approvals worldwide based on promising efficacy as a monotherapy in heavily pre-treated patients with relapsed or refractory multiple myeloma (RRMM), its standing was challenged when a pivotal confirmatory trial failed to meet its primary endpoint.[3] This led to a withdrawal of its marketing authorization in the United States and a non-renewal in the European Union.[3]

However, the therapeutic potential of belantamab mafodotin was ultimately realized through subsequent, well-designed Phase III trials evaluating its use in combination with established standards of care. These studies demonstrated profound and clinically meaningful improvements in both progression-free and overall survival, leading to a regulatory resurgence.[6] In 2025, belantamab mafodotin secured new marketing authorizations in the European Union and other key global markets for use in combination regimens, firmly re-establishing its role as a critical treatment option for patients with RRMM.[7] This report provides an exhaustive review of belantamab mafodotin, detailing its pharmacology, pharmacokinetic profile, the pivotal clinical trial data that have defined its trajectory, its unique safety considerations, and its complex global regulatory history.

Table 1: Belantamab Mafodotin Drug Profile Summary