Ophthalmic immune-related adverse events following anti-CTLA-4 or PD-1 therapy recorded in the American Academy of Ophthalmology IRIS Registry.

Abstract

e15124 Background: The detailed study of ophthalmic immune-related adverse events (OirAEs) is of integral importance in the evolving field of cancer immunotherapy to inform management and treatment guidelines. This study seeks to quantify the differences in incidence and recurrence rates of OirAEs by immune checkpoint inhibitor (ICI) status in a longitudinal big-data registry in patients who are seen in ophthalmic clinics. Methods: This retrospective registry study examined patients newly diagnosed with OirAEs between January 1, 2013 and December 31, 2017 in the American Academy of Ophthalmology’s 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 or anti-CTLA-4 therapy was determined. Incidence rate ratios (IRR) were derived by comparing incidence of OirAEs after ICIs versus rates of non-drug 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 3,123 patients were identified to have received anti-CTLA-4, anti-PD-1, or anti-PD-L1 therapy, 111 of whom developed an OirAE (3.6%). All OirAE patients had a documented initial pre-drug cancer ICD code, when available, of malignant metastatic melanoma or choroidal melanoma, with the exception of one patient. Incidence rates for anterior uveitis, the most common OirAE, were found to be 3,736 per 100,000 among all ICIs. Rates of all analyzed OirAEs among patients on ICI therapy were elevated compared to baseline ocular complication rates (IRR = 3.5 - 43.0). Time to development of OirAE was drug dependent, with anti-CTLA-4 monotherapy demonstrating rapid onset of OirAE, with most cases within 20 days of starting drug administration. Patients with a prior history of uveitis or other ocular inflammation demonstrated extremely high recurrence rates of OirAEs after initiating ICIs (51.1% for intermediate/posterior/panuveitis, 38.9% for anterior uveitis). Conclusions: Patients initiating ICI therapy are at risk of a number of ocular complications. Rates of OirAEs following ICI therapy are as high as 50% in specific patient populations, including those with a previous history of any uveitis or autoimmune ocular disease. Early coordination with ophthalmic subspecialist care, possibly before ICI is initiated, is critical for optimal care of these high risk populations.