Ocular toxicities associated with antibody drug conjugates

Area of Science:

• Oncology
• Ophthalmology
• Pharmacology

Background:

• Gynecological malignancies are treated with novel antibody-drug conjugates (ADCs).
• These ADCs are associated with specific ocular adverse effects.
• Understanding these effects is crucial for patient management.

Purpose of the Study:

• To review the structure, mechanism of action, and pathophysiology of ADCs used in gynecological cancers.
• To detail the ocular adverse effects associated with these treatments.
• To explore strategies for mitigating these side effects.

Main Methods:

• Literature review of ADCs used for gynecological malignancies.
• Analysis of reported ocular adverse events and their proposed mechanisms.
• Synthesis of current understanding of ADC-induced ocular toxicity.

Main Results:

• Tisotumab vedotin causes conjunctival toxicity (conjunctivitis, dry eye, blepharitis, keratitis) via tissue factor targeting.
• Mirvetuximab soravtansine leads to corneal toxicity (blurred vision, keratitis, dry eye) through off-target inflammation and macropinocytosis.
• Both agents demonstrate distinct patterns of ocular toxicity.

Conclusions:

• Ocular toxicity from ADCs in gynecological cancer is a significant concern.
• Mechanisms involve direct targeting (tisotumab vedotin) or off-target inflammation (mirvetuximab soravtansine).
• Multidisciplinary collaboration and mitigation protocols are essential to reduce ocular adverse events.