Ocular toxicities associated with antibody drug conjugates and immunotherapy in oncology: clinical presentation, pathogenesis, and management strategies

ABSTRACT

Introduction

The development of molecularly targeted anticancer therapies and immunotherapy continues to revolutionize the treatment of cancer. FDA accelerated approvals of novel targeted therapies allowed for introduction of these agents into the clinic at a rapid rate. On-and off-target ocular toxicities are prevalent treatment-related adverse events of newer therapies including antibody drug conjugates (ADCs) and immunotherapy. Ocular toxicities associated with ADCs and immunotherapy have heterogeneous presentations and pathogenesis requiring unique and often complex monitoring, and management.

Areas covered

In this article, we provide an updated review of treatment-emergent ocular toxicity associated with new and novel oncologic therapies and summarize guidelines and best practice strategies for prevention, monitoring and management. A literature search was performed through PubMed, ClinicalTrials.gov, and FDA website (1 January 2017 to 10 May 2023) to identify relevant information.

Expert opinion

The implementation of a strategy for monitoring, prevention, and management of treatment-related ocular toxicities involves a multi-disciplinary, often cross-center approach. Communication with infusion nursing leadership, clinic staff, and eye care providers is crucial to the successful implementation of eye care plans to prevent and manage ocular toxicity.

KEYWORDS:

• Ocular toxicities
• ocular adverse events
• eye care
• antibody drug conjugates
• immunotherapy

Article highlights

• Ocular toxicities are prevalent treatment-related adverse events of newer anticancer therapies including antibody drug conjugates (ADCs) and immune checkpoint inhibitors (ICIs).

• The clinical presentation and pathogenesis of ocular toxicities associated with anticancer therapy have heterogeneous presentations and pathogenesis, thus requiring unique and often complex monitoring and management.

• U.S. FDA approved ADCs associated with ocular toxicities include enfortumab vedotin, mirvetuximab soravtansine, and tisotumab vedotin.

• Use of prophylaxis eye drops and interval eye exams monitoring are required with mirvetuximab soravtansine and tisotumab vedotin only.

• Currently, there are ten U.S. FDA approved ICIs including nivolumab, pembrolizumab, cemiplimab, and dostarlimab, which inhibit programmed cell death 1 (PD-1) activity; atezolizumab, avelumab, and durvalumab, which inhibit PD ligand 1 (PD-L1); ipilimumab, and tremelimumab, which inhibit cytotoxic T-lymphocyte – associated antigen 4 (CTLA-4); and the new novel lymphocyte activating gene-3 (LAG-3) inhibitor, relatlimab

• Ocular toxicity associated with ICIs occur in less than 1% of patients. Uveitis and dry eye syndrome are the most commonly reported ocular immune-related adverse events (incidence, 1% to 24%). The time range to ocular toxicity onset is 2 to 65 weeks (average, 17 weeks).

• The mechanism of ICIs-associated ocular toxicity is thought to be inflammatory and related to overactivation of the immune system.

• There are no required eye exam monitoring or prophylaxis with eye drops to prevent or reduce ocular adverse events associated with ICIs.

Declaration of interests

DC Moore serves on advisory board for Pfizer, AstraZeneca, Janssen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Authors contribution statement

All authors contributed to the conception of the review article idea, literature research, and writing of the manuscript.

Additional information

Funding

This paper was not funded.