Immune checkpoint inhibitor-related pancreatitis: a comprehensive review of epidemiology, pathophysiology, and management

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but are associated with immune-related adverse events (irAEs) affecting multiple organ systems. ICI-related pancreatitis (ICI-P) is an uncommon but clinically significant toxicity with potential for irreversible pancreatic damage. This review synthesizes current evidence on the epidemiology, pathophysiology, diagnosis, and management of ICI-P. The incidence ranges from 0.5% to 5.7% depending on definitions and regimens, with combination immunotherapy conferring a significantly higher risk. Histopathologically, ICI-P is characterized by acinar-centric T cell infiltration with temporal evolution from CD4 + to CD8 + predominance. Most cases present as asymptomatic lipase elevation rather than clinical pancreatitis; however, long-term sequelae, including pancreatic atrophy (44-55%), new-onset diabetes mellitus, and exocrine insufficiency, are increasingly recognized. The role of corticosteroids remains controversial, with evidence suggesting efficacy for acute symptoms but uncertain impact on long-term outcomes. Notably, ICI-P development may be associated with improved overall survival, potentially reflecting enhanced antitumor immunity. This review provides an evidence-based framework for diagnosis and management while highlighting unresolved controversies requiring further investigation.