Risk of gastrointestinal (GI) immune-related adverse events (irAEs): Real-world experience.

e23410 Background: Immune checkpoint inhibitors (ICI) improve survival across solid tumors but can cause gastrointestinal (GI) irAEs. Real-world comparative data remains limited, particularly for composite GI outcomes. We compared the risk of GI AEs in patients receiving immunotherapy (IT) versus non-IT systemic therapy. Methods: We conducted a retrospective cohort study of 5,556 adult cancer patients treated at Cleveland Clinic Ohio between 2010–2022. Included cancers were advanced-stages bladder, endometrial, esophageal, gastric, head & neck, renal, bladder, melanoma & lung cancers, stages where IT is approved. We compared IT (± chemo/radiation) vs non-IT regimens; 99.9% of IT was ICI. Follow-up began at systemic therapy start & continued until GI-AE, death or last encounter. GI AEs included diarrhea, colitis, elevated liver enzymes, esophagitis, gastritis, enteritis, enterocolitis, & composite outcomes. Poisson regression estimated incidence rates, Kaplan–Meier methods cumulative incidence (CIR) & time-dependent Cox models (TD-HR) assessed risk with IT as a time-varying exposure. Longitudinal serum liver tests were analyzed using mixed-effects & generalized linear models over one year. Results: Among 5,556 patients, 1,288 (23%) received first-line IT & 951 (17%) second-line IT. Median age was 66 years; 38% were female & 87% White. There were 430 GI-AE & 268 entero-colonic composite events in median follow up of 14 months (CI: 6-34). Incidence rates (/100 person-years) were higher with IT for GI-AE (0.50 vs 0.27) & entero-colonic composites (0.31 vs 0.16) (P < 0.05). IT was associated with decreased esophagitis risk (TD-HR 0.26; P = 0.01). Among colitis cases, 48% were grade 2, 25% grade 3 & 18% grade 4; 89% required treatment, 46% received immunomodulators & 37% permanently discontinued therapy. Longitudinal liver analyses showed IT was associated with increased albumin (β = 0.04; P = 0.04) & decreased INR (β = −0.26; P = 0.04), with no change in ALT, AST, alkaline phosphatase, total bilirubin, or APTT. Baseline values strongly predicted longitudinal changes, & alkaline phosphatase, ALT, total bilirubin & APTT increased over time (P < 0.05). Conclusions: IT was frequently associated with GI AEs, reaching 15% at 4 years, though most were low-to-moderate grade & manageable. IT was associated with selective laboratory changes, while baseline liver values remained the strongest predictors. Lower esophagitis incidence may reflect reduced radiation exposure. Hepatic synthetic markers improved with IT. IT group (n=1,288) Non-IT group (n=4,268) Colitis: absolute number 29 28 Colitis: 2-year CIR / TD-HR TD-HR 2.5% (1.5%, 3.5%) / HR 5.2 (3.0, 9.0) 0.6% (0.4%, 0.9%) / Ref Diarrhea: absolute number 45 157 Diarrhea: CIR / TD-HR 4.3% (3.0%, 5.7%) / HR 1.4 (1.1, 1.9) 4.0% (3.3%, 4.7%) / Ref Elevated liver enzymes: absolute number 41 67 Elevated liver enzymes: CIR / TD-HR 3.8% (2.6%, 5.1%)/ HR 3.2 (2.2, 4.7) 1.7% (1.3%, 2.2%)/ Ref