Immune Checkpoint Inhibitors May Induce EPI

While they have become essential agents in treating metastatic cancers, immune checkpoint inhibitors (ICIs) are known to cause immune-related adverse events (irAE), most often diarrhea. A team of researchers sought to determine if ICIs might also be implicated in the development of exocrine pancreatic insufficiency (EPI).

Deepika Satish, MD, presented the poster, “Exocrine pancreatic insufficiency induced by immune checkpoint inhibitors: A case series,” which received a Presidential Poster Award and an Outstanding Poster Presenter award at the American College of Gastroenterology (ACG) 2020 clinical meeting and postgraduate course.

The diarrhea that affects up to 35% of patients treated with ICIs is usually attributed to colitis related to the cancer therapy. However, there have been reports of steatorrhea secondary to EPI in such cases. The researchers conducted a retrospective review of patients who had metastatic cancer who received treatment with an ICI at a tertiary care center between 2011 and 2020, and developed EPI.

The study excluded patients with pancreatic cancer, pancreatic metastases, history of pancreatic surgery, or who had used pancrelipase before receiving ICI therapy. Any patients whose records did not clearly document symptoms of EPI were also excluded. The team then identified patients whose records included an obvious description of steatorrhea that resolved upon treatment with pancrelipase.

The team found that 9 patients had developed EPI at a median of 589 (interquartile range (IQR) 149-796) days after they received their first dose of ICI. The median duration of ICI use before EPI developed was 284 (IQR 128-516) days. Some 78% of these patients had an irAE before the onset of EPI; 4 patients (44%) had multiple irAEs.

Of the 9 patients who developed EPI, 6 patients showed elevated levels of lipase before the onset of EPI; however, only 2 patients (22%) had previous episodes of pancreatitis. Among 7 of these 9 patients, fecal fat and/or elastase were tested and found to be abnormal. Cross-sectional imaging with computed tomography or magnetic resonance imaging did not reveal any characteristics of chronic pancreatitis for any of these patients. Only 1 patient had a history of alcohol abuse, but had no history of pancreatitis, while 5 patients had a history of smoking.

“EPI is a rare irAE that may develop after ICI use, even in the absence of prior clinical pancreatitis,” said Dr Satish. “Clinicians should consider this as a distinct differential diagnosis for ICI-related diarrhea, especially when the diarrhea presents later or even after the course of treatment.”


—Rebecca Mashaw



Satish D, Gerdes H, Faleck D. Exocrine pancreatic insufficiency induced by immune checkpoint inhibitors: A case series. Talk presented at: American College of Gastroenterology 2020 Clinical Meeting. October 26, 2020. Virtual.