Immune Checkpoint Inhibitor-Related Pancreatic Injury in Patients with Lung Cancer: Diagnostic Challenges, Multidisciplinary Management, and Outcomes

Background/Objectives: Immune checkpoint inhibitors (ICIs) can cause pancreatic immune-related adverse events ranging from isolated pancreatic enzyme elevation to severe acute pancreatitis. This study aimed to describe the clinical presentation, diagnostic classification, management, and outcomes of ICI-related pancreatic injury in patients with lung cancer. Methods: We conducted a retrospective, single-center case series of six patients with lung cancer who developed pancreatic injury during or after ICI treatment between January 2016 and December 2024. Clinical characteristics, laboratory and imaging findings, toxicity grade, management, and outcomes were extracted from the available medical records and analyzed descriptively. Results: The median time from ICI initiation to pancreatic injury was 8.6 months (range, 2.3–16.4 months). The recorded Common Terminology Criteria for Adverse Events (CTCAE) severity grade was 2 in two patients, 3 in one patient, and 4 in three patients; pancreatic enzyme elevations were evaluated separately from clinical pancreatic adverse-event severity. Five patients required hospitalization and received supportive care, including intravenous fluids and corticosteroids. One patient received mycophenolate mofetil, and one developed acute necrotizing pancreatitis requiring intensive care, endoscopic procedures, and repeated surgical interventions. Two patients died during follow-up. In one patient, death followed a prolonged course of severe necrotizing pancreatitis complicated by infected necrosis and multiorgan failure; in the second patient, the available retrospective records did not permit reliable attribution of the cause of death to pancreatic toxicity. Immunotherapy was resumed in two patients; recurrent pancreatic enzyme elevation occurred after rechallenge, but recurrent clinically overt pancreatitis was not documented. Conclusions: ICI-related pancreatic injury has a heterogeneous clinical presentation. Pancreatic enzyme elevation alone should not be considered equivalent to acute pancreatitis. Diagnostic classification requires integration of symptoms, biochemical findings, imaging, and exclusion of alternative etiologies. Management should be individualized, and severe cases may require early multidisciplinary involvement. The benefits of corticosteroids and routine pancreatic enzyme monitoring remain uncertain.