Clinical and Histological Characterization of Toxic Keratopathy From Depatuxizumab Mafodotin (ABT-414), an Antibody-Drug Conjugate.

Cornea
Brian A LeeJoshua H Hou

Abstract

To report the histological findings and clinical course of 2 patients with microcyst-like epithelial keratopathy (MEK) associated with antibody-drug conjugate, depatuxizumab mafodotin. Case series. Two patients with glioblastoma multiforme participating in a phase 3 clinical trial of the antibody-drug conjugate, depatuxizumab mafodotin, presented with bilateral MEK. Confocal imaging showed multiple large, round, hyperreflective lesions in the epithelium. Epithelial debridement was performed for symptomatic relief in both patients. Along with aggressive lubrication, bandage contact lenses, and reduction in the chemotherapeutic dose to maintenance levels, both patients experienced symptomatic improvement. However, MEK lesions recurred after re-epithelialization. Immunohistochemistry of the diseased epithelium showed immunoglobulin (Ig)G-positive granular cytoplasmic inclusions and increased cell apoptosis. Depatuxizumab mafodotin accumulates in the basal corneal epithelium resulting in MEK because of increased apoptosis. Frequent lubrication and bandage contact lenses can provide symptom relief.

References

Nov 1, 1982·American Journal of Ophthalmology·J H LassR H Herzig
Mar 25, 2010·Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift für Augenheilkunde·Tanja GuthoffRainer Guthoff
Nov 6, 2015·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Joshua Seth EatonChristopher J Murphy
Oct 14, 2017·Investigational New Drugs·Joanna C MastersMichael Amantea
Mar 13, 2019·Journal of the National Cancer Institute·Michael J BirrerRichard C Bates

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis