Ophthalmic Immune-related Adverse Events following anti-CTLA-4 or PD-1 Therapy Recorded in the American Academy of Ophthalmology IRIS^® Registry

Abstract

Purpose : The study of ophthalmic immune-related adverse events (OirAEs) is of integral importance in the evolving field of cancer immunotherapy. This study seeks to quantify incidence and recurrence rates of OirAEs by immune checkpoint inhibitor (ICI) status in a longitudinal big-data registry.

Methods : This retrospective registry study examined patients newly diagnosed with OirAEs between Jan 1, 2013 and Dec 31, 2017 in the American Academy of Ophthalmology IRIS^® Registry. The primary exposure of interest was prior initiation of ICIs. Incidence of OirAEs within 1 year following initiation of ICIs, including anti–PD-1 (programmed cell death 1) or anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) therapy was determined. Incidence rate ratios (IRR) were derived by comparing incidence of OirAEs after ICIs vs rates of non-immune related ocular complications in the entire registry population. Rates of OirAEs in patients with a past history of ocular inflammation or other specific ophthalmic condition prior to initiation of ICIs were further examined.

Results : A total of 3,121 patients were identified to have received anti-CTLA-4 or anti-PD-1, 70 of whom developed an OirAE. Higher rates of OirAEs were seen in the black population (8.1%) compared to whites (2.0%). Incidence rates for uveitis-specific OirAEs were found to be 5,532 per 100,000 for ipilimumab (anti-CTLA-4), 2,037 per 100,000 for nivolumab (anti–PD-1), 1,827 per 100,000 for pembrolizumab (anti–PD-1), 4,444 per 100,000 for combination ipilimumab/nivolumab, and 2,294 per 100,000 among all ICIs. In comparison to ocular complication incidence rates among all patients, rates of OirAEs among patients on ICI therapy were found to be much greater (anterior uveitis IRR=17.6, intermediate/posterior/panuveitis IRR=18.2). Among patients with a prior history of uveitis or other ocular condition anytime prior to ICI initiation, recurrence rates of ocular complications via subsequent OirAEs were high (51.1% for intermediate/posterior/panuveitis, 38.9% for anterior uveitis).

Conclusions : For patients initiating ICI therapy, early coordination with ophthalmological subspecialist care is important, as rates of OirAEs are elevated compared to ocular complication rates in the entire registry population and patients with a previous history of any uveitis or autoimmune ocular disease are at high risk of recurrence.

This is a 2020 ARVO Annual Meeting abstract.