Optimizing Belantamab Mafodotin in Relapsed or Refractory Multiple Myeloma: Impact of Dose Modifications on Adverse Events and Hematologic Response in a Real-World Retrospective Study

<b>Background</b>: Belantamab mafodotin (belamaf) is a BCMA-targeting antibody-drug conjugate used in triple-class refractory multiple myeloma. Despite its efficacy, keratopathy remains a significant dose-limiting toxicity. Following its withdrawal from the U.S. market in 2022, its use in Austria is limited to clinical trials or compassionate use. <b>Methods</b>: In this real-world, retrospective study, we analyzed 36 relapsed/refractory, BCMA-naïve multiple myeloma patients treated at the University Hospital of Vienna (January 2020-June 2024); 42% received a reduced dose (1.9 mg/kg) throughout all treatment cycles. The primary objective was to assess adverse events, particularly keratopathy, and the impact of dose modifications on toxicity and efficacy. <b>Results</b>: The overall response rate was 64%, with responders having significantly fewer prior therapy lines (median 3 vs. 4.5, <i>p</i> = 0.015). Median PFS was 7.3 months, significantly longer in responders (11.1 vs. 1.6 months, <i>p</i> < 0.0001); median OS was 20.1 months, also longer in responders (not reached vs. 18 months, <i>p</i> = 0.031). Keratopathy occurred in 75% of patients; 33% experienced grade 3-4 events. Dose reduction significantly decreased grade 3-4 keratopathy (7% vs. 52%, <i>p</i> = 0.004) and thrombocytopenia (33% vs. 67%, <i>p</i> = 0.048) without compromising efficacy. <b>Conclusions</b>: Belamaf dose reductions improved tolerability without loss of efficacy, supporting reduced dosing in practice.