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

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.