Immune Checkpoint Inhibitor-Induced Pancreatic Injury: An Emerging Form of Immune-Mediated Pancreatitis.

Abstract

Background: Immune checkpoint inhibitors (ICI) are increasingly utilized in cancer management due to their favorable outcomes. Pancreatic injury from ICIs (ICI-PI) is a heterogenous entity ranging from silent lipase elevation to clinical pancreatitis. Its distinct immunologic mechanisms and phenotype position it as a novel form of immune-mediated pancreatic injury.

Methods: We performed a narrative review of the emerging literature on ICI-PI, highlighting its mechanisms, epidemiology, clinical and imaging features, histology, management, outcomes, and critical knowledge gaps.

Results: ICI-PI often appears within months of starting therapy and frequently presents as isolated enzyme elevation rather than acute pancreatitis. Early imaging can be unremarkable, but later scans may show pancreatic volume loss or atrophy. Tissue examination shows neutrophil- and CD8-predominant infiltrates. Unlike other forms of autoimmune pancreatitis (AIP), storiform fibrosis, obliterative phlebitis, granulocytic epithelial lesions, or IgG4-rich plasma cells are not seen. Management focuses on supportive care, exclusion of alternative causes, and a temporary ICI hold for clinical pancreatitis. Corticosteroids are reasonable for symptomatic or radiographically confirmed disease, though evidence for long-term benefit is limited. Rechallenge with ICIs appears feasible in selected patients after recovery, with low recurrence rate observed in available data. Some patients develop delayed exocrine or endocrine insufficiency, underscoring the need for follow-up.

Conclusions: ICI-PI is an uncommon yet clinically important entity that shows a distinct clinicopathologic profile from other forms of AIP. Clear diagnostic criteria, practical treatment pathways, and prospective registries are needed to guide therapy, inform rechallenge decisions, and define long-term outcomes.