Belantamab Mafodotin: Ocular Toxicity and Comparative Evaluation across Antibody–Drug Conjugates

Abstract

Background: Multiple myeloma (MM) remains a therapeutic challenge, especially in relapsed or refractory disease. Belantamab mafodotin, a B-cell maturation antigen (BCMA)-directed antibody–drug conjugate (ADC), has demonstrated antimyeloma activity, but is associated with distinctive ocular toxicity.

Aim: This review summarizes the pharmacological and clinical characteristics of belantamab mafodotin, focusing on the manifestations, mechanisms, and management of its ocular toxicity, and compares its ocular safety profile with other ADCs.

Materials and Methods: A narrative literature review was conducted using PubMed. Clinical trials, real-world studies, systematic reviews, meta-analyses, and relevant mechanistic and ophthalmological studies published up to 2026 were considered.

Results: Belantamab mafodotin demonstrated clinically meaningful activity in relapsed or refractory MM. Ocular toxicity was mainly characterized by corneal epithelial abnormalities, particularly microcyst-like epithelial changes. Mechanistic evidence supports target-independent uptake by corneal epithelial cells and intracellular effects of the MMAF payload. Ocular findings commonly emerged during early treatment and required dosage modifications. Other ADCs showed heterogeneous ocular toxicity, ranging from corneal epithelial abnormalities to conjunctival and ocular surface involvement.

Conclusions: Belantamab mafodotin illustrates the importance of balancing the therapeutic potential of ADCs with tissue-specific toxicity. Ocular adverse events illustrate the interplay between ADC molecular properties and the biological characteristics of ocular tissues, highlighting this toxicity as a heterogeneous class effect. Continued investigation of tissue susceptibility and optimization of ADC design and treatment strategies may widen the therapeutic window.