1165 Spectrum of ocular immune-related adverse events and outcomes with immune checkpoint inhibitor re-treatment

<h3>Background</h3> Ocular immune-related adverse events (irAEs) are uncommon side effects of immune checkpoint inhibitor (ICI) therapy, but risk of ICI resumption following irAEs must be balanced with the potentially sight-threatening consequences of ocular irAEs. Literature on outcomes when re-trialing immunotherapy (IO) following ocular irAEs remains sparse. <h3>Methods</h3> Clinical data from adult patients who received ≥1 dose of ICI at the University of Virginia Comprehensive Cancer Center between 2013 and 2022 were retrospectively analyzed. IrAEs were graded using CTCAE v5.0 criteria. Tumor response was measured using RECIST 1.1 criteria. <h3>Results</h3> A total of 14 patients developed ≥ grade (G) 1 ocular irAEs. Median age was 65 years, M:F ratio was 1:1, and 85.7% were Caucasian (n=12). The most common cancer was melanoma (71.4%, n=10). ICI regimen included anti-PD1 alone in 4 (28.6%), anti-CTLA4 in 3 (21.4%), combination IO in 4 (28.6%), chemo-IO in 2 (14.3%), and IO plus antiangiogenic agent in 1 (7%) patient. 71.4% (n=10) received ICIs with palliative intent. The most common presenting symptoms were blurry vision (85.7%, n=12), eye pain (35.7%, n =5), and photosensitivity (21.4%, n =3). All patients received ophthalmology consultation. Median time to consultation was 3.5 days. Of the 28 eyes examined, uveitis was the most common ocular irAE (57.1%, 16 eyes). Other diagnoses included dry eye syndrome (14.3%, 4 eyes), retinal vasculitis (3.6%, 1 eye), retinal detachment (3.6%, 1 eye), and a multiple evanescent white dot syndrome-like reaction (3.6%, 1 eye). The most common ≥G3 ocular irAEs were uveitis (54.5%, 6 eyes) and dry eye syndrome (28.2%, 2 eyes). Patients received a median of 2 infusions before ocular symptom onset. IO treatment was interrupted in 8 patients (57.1%) and permanently discontinued in 3 (21.4%). 50% (n=7) were managed with topical therapy and 43% (n=6) required systemic steroids with a median duration of 33.5 days. A total of 11 patients (78.6%) resumed ICI therapy following ocular irAE. Nine (64%) experienced recurrent irAEs; two (14.3%) ocular irAEs, four (28.6%) non-ocular irAEs, and three (21.4%) with concurrent ocular and non-ocular irAEs. IO re-challenge resulted in partial response for 4 (36.4%), stable disease in 1 (9.1%), and progressive disease in 5 patients (45.5%). <h3>Conclusions</h3> ICIs can cause a broad range of ocular irAEs. Most patients tolerated ICI re-challenge following resolution of primary ocular irAEs. Early ophthalmologist and oncologist collaboration at ocular symptom onset can help improve durability of ICI therapy to the benefit of patients experiencing ocular irAEs. <h3>Ethics Approval</h3> This study was reviewed by the University of Virginia Institutional Review Board and was approved according to protocol #24436.