ArticleClinical lymphoma, myeloma & leukemia2026
Dose Delays and Treatment Interruptions Secondary to Ocular Toxicity From BCMA-Directed Antibody Drug Conjugate Therapy in Relapsed Multiple Myeloma.
Article in Clinical lymphoma, myeloma & leukemia, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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22 authors.
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Abstract
introductionUptake of BCMA-directed antibody drug conjugates (ADCs) in multiple myeloma has been hindered by ocular side-effects. Belantamab mafodotin (BelMaf) and MEDI2228 are BCMA-directed monoclonal-antibodies conjugated to the microtubule inhibitor, monomethyl auristatin F and the alkylator, pyrrolobenzodiazepine, respectively. Differences in ADC payload, antibody specificity and linker stability influence ocular toxicity. AIM/
methodsWe investigated the tolerability and ocular toxicity profiles of BCMA-directed ADC therapy. Retrospective study of 111 patients treated with BCMA-directed ADCs between 2019 and 2022.
resultsEighty-seven percent of patients were triple-class refractory, 50% penta-class refractory, 14% had prior BCMA-directed therapy and 24% extraosseous disease. Treatments included BelMaf monotherapy (n = 56), BelMaf combination therapy (n = 12) and MEDI2228 monotherapy (n = 43). The overall response rate was 30% for BelMaf and 44% for MEDI2228. Photophobia was more common with MEDI2228 (any-grade: 12% vs. 49%, P < .001), whereas keratopathy was more common with BelMaf (any-grade: 59% vs. 9%, P = .002). Four MEDI2228 recipients developed keratopathy, all grade 1 and associated with dry eyes and/or photophobia. Dose delay for ocular toxicity was comparable for BelMaf and MEDI2228 (28% vs. 19%, P = 0.2), as was the rate of dose reduction (18% vs. 12%, P = .4). The most common reasons for treatment discontinuation were progression/death (BelMaf = 71%, MEDI2228 = 44%) and ocular toxicity (BelMaf = 18%, MEDI2228 = 30%).
conclusionsTreatment interruptions, dose reductions and drug discontinuation are common with BCMA-directed ADC therapy. Research to optimize the administration schedule of these agents is warranted. BelMaf and MEDI2228 produce distinct patterns of ocular side-effects, namely keratopathy and reduced visual-acuity with the former, and photophobia and dry eyes with the latter.
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