Exocrine pancreatic insufficiency induced by immune checkpoint inhibitors Journal Article


Authors: Satish, D.; Lin, I. H.; Flory, J.; Gerdes, H.; Postow, M. A.; Faleck, D. M.
Article Title: Exocrine pancreatic insufficiency induced by immune checkpoint inhibitors
Abstract: Background: Scant data describe exocrine pancreatic insufficiency (EPI) secondary to immune checkpoint inhibitor (ICI) use. The goal of this study is to describe the incidence, risk factors, and clinical characteristics of patients with ICI-related EPI. Patients and Methods: A single center, retrospective case-control study was performed of all ICI-treated patients at Memorial Sloan Kettering Cancer Center between January 2011 and July 2020. ICI-related EPI patients had steatorrhea with or without abdominal discomfort or weight loss, started pancrelipase after initiation of ICI, and demonstrated symptomatic improvement with pancrelipase. Controls were matched 2:1 by age, race, sex, cancer type, and year of ICI start. Results: Of 12 905 ICI-treated patients, 23 patients developed ICI-related EPI and were matched to 46 controls. The incidence rate of EPI was 1.18 cases per 1000 person-years and the median onset of EPI was 390 days after the first dose of ICI. All 23 (100%) EPI cases had steatorrhea that improved with pancrelipase, 12 (52.2%) had weight loss, and 9 (39.1%) had abdominal discomfort; none had changes of chronic pancreatitis on imaging. Nine (39%) EPI patients had episodes of clinical acute pancreatitis preceding the onset of EPI, compared to 1 (2%) control (OR 18.0 (2.5-789.0), P <. 001). Finally, the EPI group exhibited higher proportions of new or worsening hyperglycemia after ICI exposure compared with the control group (9 (39.1%) vs. 3 (6.5%), P <. 01). Conclusion: ICI-related EPI is a rare but clinically significant event that should be considered in patients with late onset diarrhea after ICI treatment and often is associated with development of hyperglycemia and diabetes. © 2023 The Author(s).
Keywords: adult; controlled study; retrospective studies; major clinical study; case control study; case-control studies; hepatitis; diarrhea; monotherapy; patient selection; cancer patient; ipilimumab; ticilimumab; incidence; weight loss; smoking; medical record review; retrospective study; risk factor; abdominal pain; hyperglycemia; pneumonia; body mass; arthritis; pancreatitis; chronic pancreatitis; diabetes mellitus; colitis; cholecystectomy; alcohol consumption; cholelithiasis; diabetes; acute disease; race; adrenal insufficiency; pancrelipase; complication; hypophysitis; thyroiditis; nephritis; body weight loss; immune checkpoint inhibitor; nivolumab; humans; human; male; female; article; checkpoint inhibitor; pembrolizumab; durvalumab; steatorrhea; immune checkpoint inhibitors; atezolizumab; exocrine pancreatic insufficiency; clinical pancreatitis
Journal Title: The Oncologist
Volume: 28
Issue: 12
ISSN: 1083-7159
Publisher: Oxford University Press  
Date Published: 2023-12-01
Start Page: 1085
End Page: 1093
Language: English
DOI: 10.1093/oncolo/oyad150
PUBMED: 37285223
PROVIDER: scopus
PMCID: PMC10712706
DOI/URL:
Notes: Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is David Faleck -- Source: Scopus
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MSK Authors
  1. Hans Gerdes
    176 Gerdes
  2. Michael Andrew Postow
    361 Postow
  3. James H Flory
    69 Flory
  4. David M. Faleck
    50 Faleck
  5. I-Hsin Lin
    16 Lin
  6. Deepika Satish
    9 Satish