Clinical Report: Ocular Adverse Effects of Antibody-Drug Conjugates in Cancer Therapy
Overview
Antibody-drug conjugates (ADCs) are increasingly used in oncology due to their targeted cytotoxicity but are associated with notable ocular toxicities that can impair vision and reduce treatment adherence. This report synthesizes clinical data on ocular adverse events (AEs) linked to ADCs, explores underlying mechanisms, and discusses management strategies to mitigate these effects.
Background
ADCs combine monoclonal antibodies with cytotoxic payloads to selectively target cancer cells, minimizing systemic toxicity. Despite this precision, ocular toxicity has emerged as a significant dose-limiting adverse event, affecting patient quality of life and leading to treatment discontinuation in over half of affected cases. The payloads, mainly microtubule inhibitors and DNA-damaging agents, are primary contributors to ocular damage. Understanding the mechanisms and clinical manifestations of ADC-induced ocular toxicity is essential for improving patient outcomes.
Data Highlights
Ocular adverse events have led to premature treatment discontinuation in more than 50% of patients in clinical trials of several ADCs. The U.S. FDA has issued boxed warnings for belantamab mafodotin, tisotumab vedotin, and mirvetuximab soravtansine due to significant ocular toxicity. ADC payloads include microtubule inhibitors (e.g., auristatin, maytansinoid) and DNA-damaging agents (e.g., pyrrolobenzodiazepine, duocarmycin, calicheamicin, SN-38, DXd), both implicated in ocular adverse effects.
Key Findings
Ocular toxicity is a common and clinically significant adverse event associated with ADC therapy, often leading to treatment interruption or discontinuation.
The cytotoxic payloads, particularly microtubule inhibitors and DNA-damaging agents, are major contributors to ocular damage.
Ocular adverse events range from transient visual disturbances to potentially permanent vision loss, impacting patient quality of life.
FDA boxed warnings have been issued for certain ADCs due to their ocular toxicity profiles, underscoring the clinical importance of monitoring.
Effective management strategies including early detection, monitoring, and treatment are critical to mitigate ocular toxicity and maintain treatment adherence.
Advances in ADC design, such as optimized linker chemistry and payload selection, may reduce ocular toxicity in future therapies.
Clinical Implications
Clinicians should maintain vigilance for ocular symptoms in patients receiving ADC therapy and implement regular ophthalmologic assessments to detect early toxicity. Prompt management of ocular adverse events can prevent irreversible damage and support continued cancer treatment. Future ADC development should prioritize minimizing ocular toxicity through improved drug design and targeted delivery.
Conclusion
Ocular toxicity represents a significant challenge in the clinical use of ADCs, affecting patient quality of life and treatment continuity. A comprehensive understanding of its mechanisms and proactive management can improve outcomes and guide safer ADC development.
References
Review Article 2024 -- Ocular Adverse Effects Linked to Antibody-Drug Conjugates in Cancer Treatment
