Pancreatic involvement due to immune checkpoint inhibitors: a proposed classification

Background: Drug-induced acute pancreatitis (AP) is uncommon and pancreatic involvement due to immune checkpoint inhibitors (ICI) in published reports relied on the National Cancer Institute’s (NCI) Common Terminology Criteria for Adverse Events (CTCAE). CTCAE definition of AP differs from the revised Atlanta classification diagnostic criteria. This study aims to classify the spectrum of pancreatic involvement in patients receiving ICI therapy into categories built on the revised Atlanta classification. Methods: A retrospective cohort study of cancer patients receiving cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) inhibitors between 2011 and 2020. Pancreas-specific immune-related adverse events (irAEs) were categorized into AP and pancreatic injury. Results: Forty-seven patients on ICI therapy met selection criteria. Twenty patients (43%) had AP, while 27 (57%) had pancreatic injury. Fifteen patients (75%) developed mild AP. Five patients progressed to pancreatic atrophy, and two patients (4%) developed exocrine pancreatic insufficiency. In both groups, most patients received nivolumab therapy (70% vs. 67%, p = 0.08) with no difference in mean number of nivolumab doses (9 vs. 10, p = 0.69). There was no correlation between the mean number of nivolumab or pembrolizumab doses and AP events (OR 0.94, p = 0.26, and OR 0.98, p = 0.86), but the duration of ICI therapy was significantly related to pancreatic atrophy (OR 1.01, p = 0.05; 95% CI 1.00–1.02). Conclusion: Based on the novel classification, majority of pancreatic irAEs were classified as asymptomatic pancreatic injury but with some risk of pancreatic atrophy. This classification can help in assessing patterns of pancreatic involvement, pathogenesis, and treatment decisions.