Rare immune-related adverse events: A retrospective analysis from a single-center cohort study.

Abstract

e14615 Background: Immune checkpoint inhibitors (ICIs) have revolutionized the management of multiple malignancies. Off-target toxicity can lead to immune-related adverse events (irAEs) which can impact any organ system. Rare irAEs (r-irAEs) occur in less than 1% of patients, as defined by previous clinical trials and data-sets. Due to the rare incidence pattern of these toxicities there is a paucity of data on their work-up, management and outcomes. This study aimed to characterize our institutional experience with rare irAEs. Methods: A retrospective chart review of 2723 ICI treated patients between 2015 to 2024 within our hospital system was conducted. R-irAEs were identified to further characterize the diagnosis and treatment outcomes of these patients. Results: In total 58 patients of 2723 (2.13%) developed r-irAEs. A majority (64%) percent of them were on monotherapy, while 19% were on chemoimmunotherapy and 17% were on combination immunotherapy. The breakdown of r-irAEs by organ system is listed in table 1. Rare irAEs were most commonly found in genitourinary cancers (31%), lung cancer (28%), and melanoma (17%). Gastrointestinal toxicities were the most common (32%), followed by cardiotoxicity (21%), ocular toxicities (16%), and hematologic and endocrine toxicities, each accounting for 8.6%. Forty-one percent developed G2 toxicities, 35% (20/58) developed G3 toxicities 7% developed G4 toxicities. Overall median time from ICI exposure to rare toxicity was 7.6 months. Hematologic toxicities were the earliest to appear, on average 1.7 months after initial ICI exposure. Ocular toxicities were the most delayed r-irAE, occurring on average 11.44 months after ICI exposure. Thirty-one percent (18/58) of patients had multi-system toxicities affecting at least one other organ system. Approximately 62% (36/58) of patients received steroids for their toxicity. Of these, 42% (15/36) were re-challenged with ICI. While most patients recovered from their toxicity, myocarditis was the most fatal r-irAE, with a mortality rate of 30% due to its complications. Conclusions: Rare immune-related adverse events can be challenging to manage given lack of real-world data. Our study demonstrates that r-irAEs may occur more commonly than previously reported. Additional studies are needed to better characterize the incidence patterns and optimal management of these toxicities. Hematologic Immune tdrombocytopenia (3) Pancytopenia (1) Hemolytic Anemia (1) Endocrine Diabetes Mellitus (5) Dermatology Drug-induced hypersensitivity syndrome (1) Ocular Uveitis (5) Blepharitis (1) Optic Neuritis (2)Keratoconjunctivitis sicca (1) Rheumatology Polymyalgia rheumatica (2)Vasculitis (1) GI Mucositis (3) Pancreatitis (8)Gastritis (6)Xerostomia (2) GU Cystitis (1) CV Aortitis (1)Myocarditis (11) Neurologic Myasthenia Gravis (1) MSK Myositis (2)