S1460 Characterizing the Distribution of Immune Checkpoint Inhibitor-Induced Gastrointestinal Tract Inflammation

Introduction: Gastrointestinal immune-related adverse events (GI irAEs) remain a barrier to the successful implementation of immune checkpoint inhibitors (ICI) for advanced cancers. Lower endoscopy is the most frequently utilized diagnostic tool for GI irAEs, and the rate of upper GI inflammation is likely underestimated. We herein characterize the presentation and distribution of ICI-related biopsy-proven gastritis, duodenitis, and colitis in a large retrospective single-center cohort. Methods: From 1/1/18-12/30/23, a histopathologic diagnosis of ICI-induced GI irAE was made in 80 patients without pre-existing inflammatory GI conditions who underwent upper and lower endoscopy with biopsies of stomach, duodenum, and colon, regardless of whether their symptoms were predominantly upper or lower. Medical records were reviewed to collect oncologic history, presenting symptoms, endoscopic findings, and biopsy reports. Symptoms were characterized as “upper” (nausea, vomiting, epigastric pain, dyspepsia, reflux, belching, and early satiety) or “lower” (including diarrhea, urgency, and abdominal cramping). Luminal inflammation in stomach or duodenum was considered upper, while inflammation from cecum to anus was defined as lower. Results: Isolated upper, isolated lower, and combined upper/lower inflammation was found in 17 (21.3%), 30 (37.5%), and 33 (41.3%) patients, respectively. The culprit ICI regimen was dual anti-CTLA-4/PD-1 in 35 (43.8%) patients, anti-CTLA-4 alone in 2 (2.5%), and single agent anti-PD-(L)1 in 39 (48.8%). Patients receiving anti-CTLA-4 therapy were more likely to have upper inflammation than those on single agent anti-PD-(L)1: 32 (86.5%) vs 16 (41.0%) (P < 0.0001). Upper symptoms were 74.0% sensitive and 73.3% specific for the presence of upper GI irAE. Diarrhea was only 17.7% specific for colitis. Of 17 patients with isolated upper GI irAE, 14 (82.4%) had diarrhea at presentation, and 2 (11.8%) reported only lower symptoms. Conclusion: Upper inflammation is common among patients with GI irAEs, with higher rates among those undergoing additional blockade of CTLA-4 than PD-(L)1 alone. Many patients with upper inflammation do not report “upper” symptoms (26%), and a majority of those with only upper GI irAEs report diarrhea (82%). These data suggest that presenting symptoms poorly differentiate upper GI tract involvement in GI irAEs. In addition to lower endoscopy, esophagogastroduodenoscopy (EGD) should be considered in the evaluation of all patients with a suspected ICI-related GI irAE.