Interdisciplinary management of belantamab mafodotin-associated ocular toxicity in clinical practice

Belantamab mafodotin (BLENREP), an antibody-drug conjugate for relapsed/refractory multiple myeloma (RRMM), is associated with corneal toxicity driven by limbal stem cell dysfunction and corneal epithelial damage. We examined how keratopathy severity relates to hematologic management decisions in clinical practice.

Retrospective cohort at a tertiary referral center, including RRMM patients treated with belantamab mafodotin (2019-2022). Ophthalmic examinations were performed at baseline and before each cycle; keratopathy was graded using the Keratopathy and Visual Acuity (KVA) scale. The primary outcome was the association between KVA severity (modeled as a time-dependent covariate) and management (dose reduction, treatment holiday, or discontinuation). Secondary outcomes included predictors of severe KVA, impact of management on immediate KVA change, and timing of the first management change.

Among 41 patients (mean age 67.10 ± 11.78 years; 23/41 [56.1 %] female), 38/41 (92.68 %) developed KVA keratopathy. The median time to first KVA occurrence was 4.14 weeks, and to first management change was 7.29 weeks. Higher KVA grade was associated with earlier management change (HR 1.514; 95 % CI 1.048-2.187; p = 0.0270). At the first assessment after the initial intervention, KVA worsened after treatment holidays (+0.70 ± 0.114 grades) and improved after dose reductions (-0.20 ± 0.084; p = 0.0165). Overall, during follow-up, the most common intervention was a treatment holiday (23/37, 56.1 %), followed by dose reduction (16/37, 39.0 %) and discontinuation (6/37, 16.2 %).

KVA keratopathy occurred more frequently than in clinical trials, and nearly all patients required treatment modification. Given the strong relationship between KVA severity and management decisions, close ophthalmic monitoring from Grade 1 is warranted to mitigate progression and reduce vision-related morbidity.