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Shahar Frenkel, ABRAHAM SOLOMON, Jacob Pe'er; A novel type of corneal epitheliopathy from a new class of antibody-drug conjugate anti-cancer treatments. Invest. Ophthalmol. Vis. Sci. 2020;61(7):3633.
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Antibody-drug conjugates (ADC) is a new class of anti-cancer treatments utilizing monoclonal antibodies conjugated to cytotoxic agents by specialized chemical linkers targeting the chemotherapy to specific cancers, e.g. glioblastoma, multiple myeloma or breast cancer. The purpose of this work is to describe the ocular side effects of this new class of drugs.
A retrospective analysis of the ocular side effects in patients who received ADC either as part of clinical trials or clinical trial-related companionate use of the same drugs. We describe the phenomenon, its management, and prognosis.
Five patients (2 women) were treated with Depatux M (EGFR IGg1 monoclonal antibody conjugated to the tubulin inhibitor monomethyl auristatin F) for glioblastoma, one man was treated with Belantamab mafodotin (anti-BCMA monoclonal antibody bound to auristatin F) for multiple myeloma, and one woman for metastatic breast cancer with Trastuzumab Deruxtecan. All patients developed corneal subepithelial pseudo-microcysts that started at the limbus and migrated centripetally with only mild superficial punctate keratopathy. We interpreted these changes as a sign of a limbal stem cell (LSC) damage. The pseudo-microcysts could be best seen with retro-illumination, and could barely be noted on anterior OCT scans (Casia). Visual acuity diminished as the lesions were close to the corneal center. Vasoconstricting drops were recommended immediately prior to treatment and cold compresses during infusion to minimize side effects. Capacious lubrication helped but was insufficient. Bandage contact lenses alleviated symptoms and slightly improved visual acuity. All changes resolved within two weeks of treatment cessation.
We speculate that the findings indicate temporary damage to the limbal stem cells. It is still unclear whether the ADC by themselves damage the LSCs, is it the auristatin, or the antibodies. The release of data from animal studies conducted by the companies may shed light on the mechanism of this side effect. The growing number of ADCs requires that clinicians are aware of this side effect and its management.
This is a 2020 ARVO Annual Meeting abstract.
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