Pancreatitis and survival outcomes in immune checkpoint inhibitor–treated patients with pancreatic enzyme elevation: a single-center cohort study

Immune checkpoint inhibitor-related pancreatic injury (ICI-PI) is an uncommon immune-related adverse event ranging from isolated pancreatic enzyme elevation to overt acute pancreatitis. However, the prognostic significance of these phenotypes remains unclear. This study compared the clinical features, treatment patterns, and survival outcomes of patients with ICI-PI according to the occurrence of pancreatitis. We retrospectively included patients with malignant tumors who received immune checkpoint inhibitors and developed new-onset pancreatic enzyme elevation without an alternative cause between January 2020 and October 2025. Patients were classified as ICI-PI without pancreatitis or ICI-related acute pancreatitis according to whether they fulfilled the Revised Atlanta criteria. Overall survival (OS) was analyzed with pancreatitis treated as a time-varying exposure using Simon–Makuch curves and time-dependent Cox models. Sensitivity analyses included a restricted hepatocellular carcinoma (HCC) cohort, a tumor type-stratified Cox model, and 3- and 6-month landmark analyses. A total of 104 patients with ICI-PI were included, of whom 32 (30.8%) fulfilled the criteria for acute pancreatitis. Compared with patients with isolated pancreatic enzyme elevation, those with pancreatitis were older, had a higher proportion of non-HCC tumors and stage IV disease, and had higher mortality. Following pancreatic events, patients with pancreatitis were more likely to experience ICI interruption (75.0% vs. 18.1%, P < 0.001) and permanent discontinuation (68.8% vs. 12.5%, P < 0.001). In time-dependent Cox analysis, pancreatitis was associated with worse OS in both unadjusted analysis (HR 3.17, 95% CI 1.86–5.40; P < 0.001) and multivariable analysis (HR 3.49, 95% CI 2.05–5.94; P < 0.001). This association remained significant in the restricted HCC cohort and in the tumor type-stratified model. Landmark analyses at 3 and 6 months also showed significantly poorer subsequent survival in patients who had developed pancreatitis before the landmark time. Among patients with ICI-PI, progression to acute pancreatitis was associated with more frequent disruption of immunotherapy and significantly worse overall survival. Acute pancreatitis may represent a clinically important phenotype within pancreatic immune-related adverse events.