E0025 - Exocrine and Endocrine Pancreatic Insufficiency Induced by Immune Checkpoint Inhibitors: A Case-Control Study

Deepika Satish, MD, I-Hsin Lin, PhD, James Flory, MD, Hans Gerdes, MD, David M. Faleck, MD
Memorial Sloan Kettering Cancer Center, New York, NY

Introduction: The widespread use of immune checkpoint inhibitors (ICI) have shed light on a variety of ICI-induced pancreatic injuries. Of these, ICI-related diabetes (DM) has been recognized in multiple cases in literature, while ICI-related exocrine pancreatic insufficiency (EPI) has been recognized much less. We describe the first case-control study describing an association between EPI and worsening of glycemic control.

Methods: A single center, retrospective case-control study was performed of all patients treated with ICIs between January 2011 and July 2020. Patients with pancreas cancer, pancreas metastasis, or prior pancreatic surgery were excluded. Cases were patients with ICI-related EPI, defined as patients who started new pancrelipase after receiving ICI therapy, had clearly documented symptoms of EPI, including steatorrhea, abdominal discomfort, or weight loss, and demonstrated symptomatic improvement with pancrelipase. Controls were matched 2:1 by age, cancer type, gender, year of the first dose of ICI, and race. ICI-related hyperglycemia was defined as a new decline in glycemic control after the first dose of ICI, determined by a new HgbA1c ≥ 6.5 after the start of ICI or by initiation of new diabetes medications after ICI use.

Results: 23 patients developed ICI-related EPI and were matched to 46 controls. 9 (39.1%) patients with EPI developed new hyperglycemia after ICI use vs 3 (6.5%) controls (p < 0.01). Cases and controls had similar proportions of pre-existing diabetes prior to ICI use (2 (8.7%) vs 6 (13.0%), p = 0.92). The median time to onset of EPI was 390 days (IQR 252-578), while the median time to onset of hyperglycemia post ICI was 518 days (IQR 178-595). Notably, 7 of the 9 patients (77%) developed EPI and hyperglycemia within 10 weeks of the other. Of the EPI group, 2 patients developed new onset type 1 DM with autoantibodies, 3 patients developed acute hyperglycemia after steroid use, 2 of whom required ongoing antidiabetic agents, and 2 patients had decompensation of their pre-existing DM.

Discussion: There are multiple phenotypes of hyperglycemia that can manifest after ICI therapy. The majority of these patients displayed loss of glycemic control within weeks of exhibiting symptoms of EPI. This is highly suggestive that there can be concurrent loss of endocrine and exocrine pancreatic function secondary to ICI use.



Disclosures:


Deepika Satish, MD, I-Hsin Lin, PhD, James Flory, MD, Hans Gerdes, MD, David M. Faleck, MD. E0025 - Exocrine and Endocrine Pancreatic Insufficiency Induced by Immune Checkpoint Inhibitors: A Case-Control Study, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.