S3412 Diagnostic Workup for Pancreatic Immune-Related Adverse Events: A Case Series From a Tertiary Care Center

Introduction: Immune checkpoint inhibitors (ICIs) have become the standard of care across a multitude of malignancies. Immune-related adverse events (irAEs) result from off-target inflammation from autoreactive T-cells. Inflammation of the pancreas is a rare irAE with the potential to have significant morbidity. The National Comprehensive Cancer Network (NCCN) provides guidelines for the assessment/grading of asymptomatic pancreatic enzyme elevation and acute pancreatitis. However, the diagnostic criteria for pancreatic irAEs remain poorly defined due to the paucity of cases. Case Description/Methods: Records from a tertiary care center were manually reviewed to identify patients who received ICIs between 2015 and 2024. Of 2,723 patients on ICIs, 9 patients presented with suspected pancreatic irAE. The median age was 68 years old. Malignancies included melanoma (n = 5), renal cell carcinoma (n = 2), lung adenocarcinoma (n = 1), and urothelial carcinoma (n = 1). Immune checkpoint inhibitor regimens included nivolumab/ipilimumab (n = 3), pembrolizumab monotherapy (n = 4), and nivolumab monotherapy (n = 2). Seven patients had additional irAEs reported, most commonly colitis (n = 4), dermatitis (n = 2), and mucositis (n = 2). The median time from ICI initiation to pancreatic irAE diagnosis was 210 days, with a median of 10 ICI cycles administered. Five patients were admitted to the hospital for evaluation. Active alcohol use was reported in 5 cases. Four patients were asymptomatic; 5 had abdominal symptoms. Four patients did not have triglyceride levels tested and 8 did not have IgG4 levels tested at the time of diagnosis. In addition, 3 patients had negative computed tomography readings, but 2 of these had positron emission tomography (PET) scans suggestive of pancreatitis. Overall, only 2 patients received GI consultation, 1 inpatient and the other outpatient. Discussion: This case series underscores the diagnostic challenges of pancreatic immune-related adverse events (irAEs) in patients receiving ICIs. Despite existing guidelines, gaps in practice—such as omitted triglyceride and IgG4 testing, limited imaging, and infrequent GI consultation—highlight the need for more consistent evaluation. Improved use of computed tomography imaging, early multidisciplinary input, and standardized diagnostic pathways could enhance care. Strengthening the diagnostic approach is essential for timely management and for informing future prospective studies on this rare toxicity.