Association of immune checkpoint inhibitors with increased pancreatitis risk in gastrointestinal cancers: A propensity-matched real-world analysis.

e16498 Background: Immune checkpoint inhibitors (ICIs) are widely used in gastrointestinal (GI) malignancies but are associated with immune-related toxicities, including pancreatitis. Comparative real-world data evaluating pancreatitis risk following ICIs versus chemotherapy are limited. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network (2015–2025) including adults with GI malignancies treated with ICIs or chemotherapy. Patients with non–treatment-related pancreatitis were excluded. The primary outcome was acute pancreatitis at 3 months, 6 months, and 1 year. Secondary outcomes included mortality, ICU admission, pneumonia, colitis, and gastrointestinal surgery at 1 year. Propensity score matching was applied. Results: After matching, 34,021 patients were included in each cohort. ICI therapy was associated with a significantly higher risk of acute pancreatitis at 3 months (0.4% vs 0.2%; RR 1.67), 6 months (0.6% vs 0.3%; RR 1.70), and 1 year (0.9% vs 0.5%; RR 1.65; all p < 0.001). At 1 year, ICIs were also associated with higher mortality (35.1% vs 23.8%; HR 1.66) and higher gastrointestinal surgery rates (13.5% vs 9.8%; RR 1.39), but lower ICU admission (RR 0.82), pneumonia (RR 0.94), and coded noninfectious colitis (RR 0.86). Conclusions: In this large real-world analysis, ICIs were associated with a significantly increased and persistent risk of acute pancreatitis compared with chemotherapy, along with higher mortality and GI surgical burden. These findings support pancreatitis as a clinically relevant immune-related adverse event and underscore the need for vigilant pancreatic monitoring in GI cancer patients receiving ICIs.