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Characterization of Belantamab Mafodotin-Induced Corneal Changes in Patients With Multiple Myeloma
Vivian Lee1, Malin Hultcrantz2, Stephanie Petrone3
1Department of Ophthalmology and Scheie Eye Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia.
Importance:
Ocular surface events are a class effect of microtubule-inhibitor payload-containing antibody-drug conjugates (ADCs); the mechanism underlying these events has not been fully elucidated.
Objective:
To characterize corneal epithelial changes in patients with relapsed or refractory multiple myeloma (RRMM) treated with belantamab mafodotin, a maleimidocaproyl monomethyl auristatin-F (MMAF)-containing ADC.
Design, Setting, And Participants:
This multicenter, phase 3b case series study was conducted in the US from March 26, 2020, to November 21, 2022, among adults with RRMM. Data were analyzed from May 2021 to May 2023.
Exposure:
Prior or ongoing treatment with belantamab mafodotin.
Main Outcomes And Measures:
The primary end point included pathologic characteristics and composition of corneal epithelial changes obtained by impression cytology (IC) or superficial keratectomy (SK) in patients treated with belantamab mafodotin. Tear film and blood were collected to determine belantamab mafodotin concentrations in patients at the time of sampling.
Results:
Of 16 patients screened, 9 were included in this study, with 6 evaluable corneal samples obtained from 6 patients either by IC (n = 4) or SK (n = 2). Of 9 patients included, median (range) patient age was 67.0 (57.0-81.0) years for those with samples obtained by IC and 68.0 (65.0-81.0) years for those with samples obtained by SK. Six patients (67%) were female. All samples demonstrated epithelial cells with eosinophilic intracytoplasmic inclusions, basophilic granular cytoplasm, or both. Five samples were positive for apoptosis, and 3 samples showed evidence of inflammation. All patients experienced complete IC or SK wound healing. ADC was detected in the tear fluid of 5 of 7 patients with tear fluid sampling, while ADC was quantifiable in 3 of 4 patients with blood samples.
Conclusions And Relevance:
In this case series study, intracytoplasmic inclusions were observed by histopathology in the corneal epithelium of patients exposed to belantamab mafodotin, and the pattern of corneal changes suggests limbal vessels may be a primary pathway enabling ADC to reach the cornea. Although limited to 6 samples, this study helps us better understand corneal changes associated with certain ADCs.
Trial Registration:
ClinicalTrials.gov Identifier: NCT04549363.
Insights
Ocular surface events are common with antibody-drug conjugates (ADCs). This study found intracytoplasmic inclusions in corneal epithelium of patients treated with belantamab mafodotin, suggesting limbal vessels may facilitate ADC delivery to the cornea.
Area of Science:
- Ophthalmology
- Oncology
- Pharmacology
Background:
- Ocular surface events are a known class effect of microtubule-inhibitor antibody-drug conjugates (ADCs).
- The precise mechanism driving these ocular events remains incompletely understood.
- Belantamab mafodotin, a novel ADC, is used for relapsed or refractory multiple myeloma (RRMM).
Purpose of the Study:
- To characterize the corneal epithelial changes in patients with RRMM undergoing treatment with belantamab mafodotin.
- To investigate the potential pathways of ADC penetration into corneal tissues.
Main Methods:
- A multicenter, phase 3b case series involving adults with RRMM treated with belantamab mafodotin.
- Corneal epithelial samples were obtained via impression cytology (IC) or superficial keratectomy (SK).
- Histopathological analysis of corneal tissues, alongside tear film and blood sampling for ADC concentration determination.
Main Results:
- All 6 evaluable corneal samples exhibited epithelial cells with intracytoplasmic inclusions, indicative of cellular changes.
- Apoptosis was observed in 5 samples, and inflammation in 3 samples.
- Belantamab mafodotin was detected in the tear fluid of 5/7 patients and quantifiable in the blood of 3/4 patients.
Conclusions:
- Histopathological examination revealed intracytoplasmic inclusions in the corneal epithelium of patients exposed to belantamab mafodotin.
- Findings suggest that limbal vasculature may serve as a key route for ADC entry into the cornea.
- This study contributes to understanding the ocular side effects associated with specific ADCs.
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