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[米伐妥昔单抗索拉坦辛的角膜事件:与微管蛋白作用抗体药物偶联物米伐妥昔单抗索拉坦辛相关的眼表事件综述]

[Corneal events with mirvetuximab soravtansine : A review of ocular surface events associated with the tubulin-acting antibody-drug conjugate, mirvetuximab soravtansine].

作者信息

Khoramnia Ramin, Schmidinger Gerald

机构信息

Klinik und Poliklinik für Augenheilkunde, Universitätsklinikum Carl Gustav Carus, TU Dresden, Fetscherstr. 74, 01307, Dresden, Deutschland.

Universitätsklinik für Augenheilkunde, Medizinische Universität Wien, Wien, Österreich.

出版信息

Ophthalmologie. 2025 Sep 2. doi: 10.1007/s00347-025-02306-7.

Abstract

Antibody-drug conjugates (ADC) are a class of targeted anticancer therapy that consist of a monoclonal antibody (linker) and a cytotoxic substance. Ocular adverse events (AEs) are common among ADCs with tubulin-targeted active agents, such as belantamab mafodotin, tisotumab vedotin and mirvetuximab soravtansine (MIRV). The substance MIRV targets folate receptor alpha (FRalpha) and has a tubulin-acting agent (the maytansinoid DM4). The use of MIRV received full approval in the USA (March 2024) for FRalpha-positive platinum-resistant ovarian cancer (PROC) and is the first novel agent to demonstrate a significant survival advantage against single agent chemotherapy in a phase 3 PROC trial. The use of MIRV was recently approved by the European Medicines Agency (EMA) for the same indication, as assessed in the MIRASOL trial. Ocular AEs associated with MIRV primarily include blurred vision and keratopathy, due to transient corneal alterations; however, the mechanism by which MIRV causes ocular AEs is thought to be a result of "off-target" effects or non-specific uptake by corneal epithelial cells. Results from clinical trials of MIRV demonstrate that these AEs can be resolved and monitoring/prophylactic strategies are in place to mitigate their incidence, including prophylactic corticosteroid eye drops, daily lubricating eye drops, dose modifications and regular ocular examinations. Support from ophthalmologists is essential to AE management to allow MIRV therapy to continue. This review provides ophthalmologists with a clinical overview of ocular AEs associated with certain tubulin-acting ADCs, with a focus on MIRV, and the prophylactic/mitigative measures that can allow patients to stay on MIRV therapy longer.

摘要

抗体药物偶联物(ADC)是一类靶向抗癌疗法,由单克隆抗体(连接子)和细胞毒性物质组成。眼部不良事件(AE)在使用微管蛋白靶向活性剂的ADC中很常见,如贝兰他单抗马福多汀、替索单抗维托辛和 mirvetuximab soravtansine(MIRV)。MIRV 靶向叶酸受体α(FRα),并具有一种微管蛋白作用剂(美登素类 DM4)。MIRV 于 2024 年 3 月在美国获得全面批准,用于治疗 FRα 阳性铂耐药卵巢癌(PROC),并且是首个在 3 期 PROC 试验中显示出相对于单药化疗具有显著生存优势的新型药物。最近,欧洲药品管理局(EMA)根据 MIRASOL 试验的评估结果,批准 MIRV 用于相同适应症。与 MIRV 相关的眼部 AE 主要包括视力模糊和角膜病变,这是由于角膜短暂改变所致;然而,MIRV 导致眼部 AE 的机制被认为是“脱靶”效应或角膜上皮细胞非特异性摄取的结果。MIRV 的临床试验结果表明,这些 AE 是可以解决的,并且已经制定了监测/预防策略以降低其发生率,包括预防性使用皮质类固醇眼药水、每日使用润滑眼药水、调整剂量以及定期进行眼部检查。眼科医生的支持对于 AE 的管理至关重要,以便 MIRV 治疗能够继续进行。本综述为眼科医生提供了与某些微管蛋白作用 ADC 相关的眼部 AE 的临床概述,重点是 MIRV,以及可以使患者更长时间接受 MIRV 治疗的预防/缓解措施。

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