Real-world data on clinical profile of immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) in oncology.

11151 Background: Immune checkpoint inhibitors (ICIs) are widely used in cancer, and are associated with immune-related adverse events (irAEs) in many organs. Real-world data on the spectrum, timing, severity, and outcomes of irAEs is limited. In this study, we aimed to gather real world data on the immune toxicity of ICIs. Methods: We conducted a retrospective cohort study on adult oncology patients on ICI therapy between Jan 2018-Dec 2024. IrAEs were categorized by organ system, time to onset (early < 12 weeks, intermediate 12-24 weeks, and late > 24 weeks), and severity (standard toxicity criteria CTCAEv6.0). Management strategies, therapy discontinuations, hospitalizations, and survival were assessed. Results: We screened 652 patients who received ICIs across different cancer types -169 (26%) were identified with irAEs. Sixty-four percent patients had received ICI alone, and the remainder had received ICIs in combination with other agents. The most common organ affected was thyroid (43%), followed by skin (28.4%), and lung (11.8%), more than one organ was affected in 22.5% patients. IrAEs occurred across a broad time frame following treatment- cumulative incidence before 12 weeks was 41.4%, between 12-24 weeks was 44.4%, and beyond 24 weeks was 91.3%. Musculoskeletal, hepatic, pulmonary, gastrointestinal, dermatologic, and pancreatic irAEs generally presented early, with median onset around 10–14 weeks. Renal, ophthalmologic, infusional, and dermatologic irAEs generally occurred across early, and intermediate time frames, while neurological irAEs tended to occur late. Endocrine irAEs, had a median onset of 20.1 weeks, and frequently occurred beyond 24 weeks. Hepatitis, pneumonitis, colitis, CNS and pancreatic toxicity were among the more severe irAEs, with a median CTCAE grade of 3, while renal, endocrine, ophthalmologic, infusional, and dermatologic irAEs were generally of lower severity (grade 1 or 2). IrAE grade > 2 was associated with increased risk of death (HR 2.7, 95% CI 1.1-6.5). Management of irAEs comprised supportive care alone (62%), systemic corticosteroids (31%), or observation alone (8%). Patients with higher grades of irAEs were more likely to receive steroids. Hospitalization was required in 29%, and ICIs were permanently discontinued in 25%. Complete resolution of irAEs was seen in 40%, 5% died attributable to the irAE, and the remainder had partial resolution of irAE with need for continued replacement therapy (as with endocrine irAEs). Conclusions: In our real-world practice, oncology patients receiving ICIs had irAEs across a broad range of organ systems, with heterogeneous timing and severity. Several clinically meaningful toxicities presented late in the treatment course, underscoring the importance of long-term monitoring. Occurrence of grade 2 or higher iRAEs was associated with higher mortality.