Ocular Toxicity Appears Common With Belantamab Mafodotin in Advanced Multiple Myeloma

Three-quarters of a small cohort of patients with advanced multiple myeloma (MM) developed ocular toxicity with belantamab mafodotin (BLMF), according to the results of a retrospective study published in the British Journal of Haematology.

BLMF is a BCMA-targeted antibody-drug conjugate with a monomethyl auristatin F payload that is approved for the treatment of advanced MM. Ocular toxicity was commonly observed in clinical trials, which has required BLMF to be available only through a risk evaluation and mitigation strategy program. The aim of this study was to evaluate the effect of BLMF-associated ocular toxicity on patient outcomes.

The single-center, retrospective study evaluated data from 38 consecutive patients with advanced MM who were treated with BLMF between January 2020 and January 2021 outside of a clinical trial. All patients underwent an ophthalmic examination prior to treatment initiation. Patients were to avoid using contact lenses and to administer lubricant eye drops at least 4 times per day during treatment.

At baseline, the median age was 67, 66% of patients were male, and 89% had high-risk disease. The median prior lines of therapy before initiating BLMF was 8 (range, 2-15), with the median duration between MM diagnosis and BLMF of 7 years. Patients received a median of 4 BLMF doses (range, 1-14) and the median follow-up was 11 months.

Ocular toxicity occurred among 75% of patients. There were also 69% of patients who developed keratopathy, including 14% that were grade 3 in severity. Keratopathy most commonly occurred after cycle 1 (36%) or cycle 2 (28%) within a median of 1.4 months. Withholding BLMF resulted in keratopathy improvement within a median of 2.4 months.

“We also observed that patients who responded to BLMF developed ocular toxicities early in their disease course compared to the non-responders,” the authors wrote in their report.

Treatment discontinuation due to keratopathy occurred among 14% of patients, 11% required a dose reduction, and 25% had a dose delay. There were 70% of patients who required treatment delay or discontinuation who developed MM progression within a median 3 months.

“Our study could not assess the implications of ocular toxicity on the patients’ quality of life” due to the retrospective design, the authors wrote.

The overall response rate to BLMF was 29%, which included 3 very good partial responses. The median progression-free survival was 2 months with an overall survival of a median 7.2 months.

The authors concluded that “while frequent ocular toxicity-related interruptions occurred at an expected rate in the current study, keratopathy-related permanent treatment discontinuation was observed in higher proportion of patients than that encountered in the DREAMM-2 trial.” They added that “until adequate measures to successfully prevent and mitigate ocular toxicity are developed, and eventually adopted, the full potential of this promising agent cannot be realized.”

Disclosures: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Abeykoon JP, Vaxman J, Patel SV, et al. Impact of belantamab mafodotin-induced ocular toxicity on outcomes of patients with advanced multiple myeloma. Br J Haematol. Published online June 13, 2022. doi: 10.1111/bjh.18298

This article originally appeared on Hematology Advisor