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Clinical Trial
. 2025 Jun 1;143(6):507-514.
doi: 10.1001/jamaophthalmol.2025.1008.

Characterization of Belantamab Mafodotin-Induced Corneal Changes in Patients With Multiple Myeloma

Vivian Lee  1 , Malin Hultcrantz  2 , Stephanie Petrone  3 , Eric W Lewis  4 , Hussam Banna  5 , Eben Lichtman  6 , Praneetha Thulasi  7   8 , Anjulie A Quick  9 , Bennie H Jeng  10   11 , Sarah B Sunshine  10 , Jasmine H Francis  12 , Julia Canestraro  12 , Asim V Farooq  13 , Peter Clements  14 , Nicola Robertson  15 , Mark Burman  16 , Tom McKevitt  14   17 , Herbert Struemper  18 , Lucinda Weir  15
Affiliations
Clinical Trial

Characterization of Belantamab Mafodotin-Induced Corneal Changes in Patients With Multiple Myeloma

Vivian Lee et al. JAMA Ophthalmol. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Lee reported receiving the Yanoff endowment from Drexel University and unrestricted departmental funds from Research to Prevent Blindness during the conduct of the study and personal fees from GSK outside the submitted work. Dr Hultcrantz reported research funding from GSK and funding support for this publication from the Memorial Sloan Kettering Core Grant (P30 CA008748) during the conduct of the study and research funding from AbbVie, Beigene, Bristol Myers Squibb, Cosette Pharmaceuticals, Daiichi Sankyo, GSK, Johnson & Johnson, Springworks Therapeutics, and The Binding Site outside the submitted work. Dr Petrone reported consulting fees from the Association of Community Cancer Centers, Bristol Myers Squibb, GSK, OnCusp Therapeutics, and WIRB-Copernicus Group outside the submitted work. Dr Lewis reported serving as an employee of and holding financial equities in GSK both during the conduct of the study and outside the submitted work. Dr Lichtman reported personal fees from AbbVie, ChemoCentryx, Eli Lilly, Novartis, and UCB outside the submitted work. Dr Thulasi reported personal fees from Sanofi outside the submitted work. Dr Jeng reported personal fees from GSK both during the conduct of the study and outside the submitted work. Dr Sunshine reported personal fees from AstraZeneca and GSK outside the submitted work. Dr Farooq reported consultancy for Ambrx, Amgen, Eisai, GSK, Immunogen, Mythic Therapeutics, Sanofi, Santen, Seagen, Skye Bioscience, and Vicore Pharma and serving on a data monitoring committee for AstraZeneca outside the submitted work. Drs Clements, Struemper, and Weir reported employment by and holding shares in GSK during the conduct of the study. Ms Robertson is an employee of and holds financial equities in GSK. Dr McKevitt is a former employee of and holds financial equities in GSK. Mr Burman reported holding shares in GSK outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Representative Images From Impression Cytology Procedures
A, Micrograph demonstrating eosinophilic intracytoplasmic inclusion (arrowhead) in case 1; scale bar represents 100 μm. B, Micrograph from case 2 demonstrating eosinophilic inclusions (arrowheads); scale bar represents 100 μm. C, Micrograph demonstrating eosinophilic intracytoplasmic inclusions and few lymphocytes from case 3; arrowheads indicate apoptotic cells. D, Micrograph demonstrating eosinophilic intracytoplasmic inclusions (arrowhead) from case 4; scale bar represents 100 μm. All micrographs were hematoxylin-eosin stained.
Figure 2.
Figure 2.. Representative Images From Superficial Keratectomy Procedures for Case 6
A, Micrograph demonstrating hematoxylin-eosin–stained corneal epithelial biopsies; scale bar represents 100 μm. Yellow arrowheads indicate eosinophilic inclusions, with pink arrowheads indicating apoptotic cells. B, Fluorescent micrograph following transferase dUTP nick-end labeling (TUNEL) staining (green) evidencing apoptotic cells in corneal epithelial tissues. C, Hematoxylin-eosin–stained corneal epithelial biopsy demonstrating cell with amphophilic, granular cytoplasm (arrowhead). D, Immunoglobulin G (IgG) immunohistochemistry shows evidence of intracytoplasmic inclusions staining positive for IgG. The arrowheads indicate cells with intracytoplasmic inclusions positive for IgG.
See this image and copyright information in PMC

Comment in

  • Corneal Changes From Antibody-Drug Conjugates.
    Dalvin LA, Berkenstock MK, Pasricha ND. Dalvin LA, et al. JAMA Ophthalmol. 2025 Jun 1;143(6):515-516. doi: 10.1001/jamaophthalmol.2025.1135. JAMA Ophthalmol. 2025. PMID: 40338592 No abstract available.

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