Incidence of Pancreatic Injury and Pancreatitis in Patients Treated With Immune Checkpoint Inhibitors
Yasuki Hori, Itaru Naitoh, Aya Naiki‐Ito, Tatsuya Kawai, Michihiro Yoshida, Akihisa Kato, Kenta Kachi, Hidenori Sahashi, Akihisa Adachi, Tadashi Toyohara, Yusuke Kito, Tatsuhito Yamamoto, Satoru Takahashi, Hiromi Kataoka
Abstract
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.