Clinical lymphoma, myeloma & leukemia · 2026
Dose Delays and Treatment Interruptions Secondary to Ocular Toxicity From BCMA-Directed Antibody Drug Conjugate Therapy in Relapsed Multiple Myeloma.
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Rees MJ, Xu TT, Atallah-Yunes SA, Lim KJC, Ailawadhi S, Parrondo R, Fonseca R, Bergsagel PL, Hayman S, Dispenzieri A, Buadi F, Dingli D, Warsame R, Kapoor P, Abeykoon JP, Gertz MA, Muchtar E, Kourelis T, Gonsalves W, Rajkumar SV, Patel SV, Kumar S
Аннотация
INTRODUCTION: Uptake 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/METHODS: We 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.
RESULTS: Eighty-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%).
CONCLUSIONS: Treatment 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.
AIM/METHODS: We 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.
RESULTS: Eighty-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%).
CONCLUSIONS: Treatment 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.