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抗体药物偶联物 Depatuxizumab Mafodotin(ABT-414)所致中毒性角膜病变的临床和组织学特征

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

作者信息

Lee Brian A, Lee Michael S, Maltry Amanda C, Hou Joshua H

机构信息

Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN.

出版信息

Cornea. 2021 Sep 1;40(9):1197-1200. doi: 10.1097/ICO.0000000000002595.

Abstract

PURPOSE

To report the histological findings and clinical course of 2 patients with microcyst-like epithelial keratopathy (MEK) associated with antibody-drug conjugate, depatuxizumab mafodotin.

METHODS

Case series.

RESULTS

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.

CONCLUSIONS

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.

摘要

目的

报告2例与抗体药物偶联物地帕妥昔单抗莫福汀相关的微囊样上皮性角膜病变(MEK)患者的组织学检查结果及临床病程。

方法

病例系列研究。

结果

2例多形性胶质母细胞瘤患者参与了抗体药物偶联物地帕妥昔单抗莫福汀的3期临床试验,均出现双侧MEK。共聚焦成像显示上皮层有多个大的、圆形的、高反射性病变。对2例患者均进行了上皮清创术以缓解症状。除积极使用润滑剂、佩戴绷带角膜接触镜并将化疗剂量降至维持水平外,2例患者的症状均有改善。然而,上皮再形成后MEK病变复发。病变上皮的免疫组织化学显示免疫球蛋白(Ig)G阳性的颗粒状胞质内含物及细胞凋亡增加。

结论

地帕妥昔单抗莫福汀因凋亡增加而在角膜基底上皮中蓄积,导致MEK。频繁使用润滑剂和佩戴绷带角膜接触镜可缓解症状。

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