Incidence of Pancreatic Injury and Pancreatitis in Patients Treated With Immune Checkpoint Inhibitors

INTRODUCTION:Immune checkpoint inhibitors (ICIs) are being increasingly used to treat advanced malignancies. ICI-induced pancreatic injury (ICI-PI), which is an immune-related adverse event that may be a risk factor of ICI-associated pancreatitis, is not well documented in the literature.METHODS:Consecutive patients who received ICIs for advanced malignancies from August 2015 through October 2022 were analyzed for the incidence of ICI-PI based on the Common Terminology Criteria for Adverse Events and ICI-associated pancreatitis. The imaging, clinical, and pathological findings of ICI-associated pancreatitis were also assessed.RESULTS:This study enrolled 843 patients. In multivariable analyses, dual or simultaneous immunotherapy and >= 10 cycles of ICI administration were significant predictive factors for all grades of pancreatic injury, including grade >= 3. Notably, patients who received simultaneous immunotherapy exhibited a higher incidence of grade >= 3 pancreatic injuries compared with those receiving asynchronous immunotherapy in univariable analysis (P = 0.032). One-fifth of the patients (16/70) with grade >= 3 pancreatic injuries had imaging evidence of pancreatitis similar to mild acute pancreatitis. ICI-associated pancreatitis was observed in 5.7% (48/843) of patients, including 1.8% (15/843) with moderate-to-severe pancreatitis (grade >= 2). Symptomatic cases (0.36%, 3/843) were treated with steroids with favorable outcomes. Immunohistochemistry for CD4 and CD8 revealed greater infiltration of CD8+ than CD4+ lymphocytes.DISCUSSION:Simultaneous immunotherapy and dual immunotherapy are risk factors of ICI-PI. Although most patients diagnosed with ICI-PI and ICI-associated pancreatitis were asymptomatic and had a low mortality likelihood, long-term outcomes, including endocrine and exocrine function, should be carefully monitored.