P2111 - Pancreatic Insufficiency and Time to Disease Progression Following Immune Checkpoint Inhibitor Pancreatic Injury in Advanced Cancers

Award: Presidential Poster Award

Award: Presidential Poster Award

Matthew J. Townsend, MD, MSc, MPP¹, Mofei Liu, MSPH², Anita Giobbie-Hurder, MS², Jordan S. Sack, MD, MPH³, Osama E. Rahma, MD², Julia McNabb-Baltar, MD, MPH⁴, Shilpa Grover, MD, MPH^5
1Harvard Medical School, Durham, NC; ²Dana Farber Cancer Institute, Boston, MA; ³Icahn School of Medicine at Mount Sinai, New York, NY; ⁴Brigham & Women's Hospital, Dana Farber Cancer Institute, Boston, MA; ⁵Brigham & Women's Hospital, Boston, MA

Introduction: Immune checkpoint inhibitor-induced pancreatic injury (ICI-PI) ranges in presentation from asymptomatic enzyme elevation to symptomatic acute pancreatitis. Long-term outcomes of these patients remain poorly defined. This study characterizes progression-free survival and development of exocrine and endocrine pancreatic insufficiency after ICI-PI.

Methods: We retrospectively queried all cancer patients at our institution who received one or more doses of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor, programmed cell death-1 (PD-1)/PD-1 ligand (PD-L1) inhibitor or both between 2011 and 2019 and later had at least one serum lipase elevation. Two physicians including a pancreatologist assessed cases to confirm ICI-induced pancreatic injury after ruling out all other etiologies. Exocrine pancreatic insufficiency was defined by fecal elastase (< 200ug/g) and new need for pancreatic enzyme supplementation. Endocrine insufficiency was defined by new-onset diabetes mellitus.

Results: Of 6450 patients treated with ICI, 364 (6%) had elevated serum lipase while on ICI therapy. Of these, 105 (29%) had ICI-PI of which 12 (11%) developed pancreatic insufficiency: three (3%) with exocrine insufficiency and 9 (9%) with endocrine insufficiency over a median follow-up of 673 days. All patients with exocrine insufficiency and four with endocrine insufficiency occurred among the 27 (26%) ICI-PI patients that met Atlanta criteria for acute pancreatitis. No patient with pancreatic insufficiency had pre-ICI hyperlipasemia, pancreatic metastasis, abdominal radiation, or evidence of chronic pancreatitis on subsequent scans. ICI-PI patients manifesting as acute pancreatitis were significantly more likely than ICI-PI patients without acute pancreatitis to have pancreatic exocrine insufficiency (11% vs 0%, p=0.02) and persistent/recurrent hyperlipasemia (56% vs 17%, p< 0.01) but not endocrine insufficiency (15% vs 6%, p=0.23)(Table 1). As compared with non-ICI injury, patients with any ICI-PI had 49% lower hazard of disease progression (HR 0.51, 95% CI:0.35-0.76, p< 0.01) and longer median time to progression (41.7 vs 14.3 months)(Image 1). Patients with ICI-induced acute pancreatitis had trend toward reduction in hazard of disease progression compared to patients without pancreatitis (HR 0.63, 95% CI:0.38-1.07, p=0.08).

Discussion: Patients with acute ICI pancreatitis should be monitored for exocrine pancreatic insufficiency. The presence of any ICI-PI may portend lower hazard of disease progression.




Disclosures:


Matthew J. Townsend, MD, MSc, MPP¹, Mofei Liu, MSPH², Anita Giobbie-Hurder, MS², Jordan S. Sack, MD, MPH³, Osama E. Rahma, MD², Julia McNabb-Baltar, MD, MPH⁴, Shilpa Grover, MD, MPH⁵. P2111 - Pancreatic Insufficiency and Time to Disease Progression Following Immune Checkpoint Inhibitor Pancreatic Injury in Advanced Cancers, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.