The Constellation of Upper Gastrointestinal Symptoms and Associated Endoscopic and Histologic Features in Patients Receiving Immune Checkpoint Inhibitors

Abstract

Introduction: Background: Immune checkpoint inhibitors (ICPIs) have demonstrated high effectiveness in treating advanced malignancies. Gastrointestinal (GI) adverse events involving the lower GI tract are commonly reported, however, very limited data is available about upper GI tract toxicities. We aimed to describe clinical, endoscopic and histological characteristics of upper GI tract injury related to ICPI treatment. Methods: We studied consecutive patients who developed upper GI symptoms requiring esophagogastroduodenoscopy (EGD) within 6 months of ICPI treatment (4/2011—3/2018). Results: Sixty patients met inclusion criteria; 92% Caucasians, 68% males with mean age of 59 years. The proportion of patients on CTLA—4 based therapy was comparable to that of PD—1/L1 (Table 1). The most common presenting symptoms were nausea and vomiting (78%). Eleven patients suffered from symptoms of upper GI bleeding. Mean time from ICPI initiation to onset of injury was 5 months. Endoscopically, mucosal ulceration was evident in 7 (12%) patients and non—ulcerative inflammation in 34 (57%). Histologic inflammation of the stomach was evident in 83% of patients, and of the duodenum in 38%. Risk factors for gastritis such as chemotherapy, radiotherapy, and non—steroidal anti—inflammatory drugs within 3 months of onset were recorded in 42 patients. Patients without these risk factors had isolated gastric involvement on endoscopy (Table 2). The rate of ulceration was the same in the cohorts with and without other risk factors (11% vs. 12%). Among patients with concurrent colonoscopies, endoscopic inflammation involving both upper and lower GI tract was detected in 21 (Table 3). Upper GI injury was treated with proton pump inhibitors or H2—blockers (n = 54), steroids (n = 25), and infliximab or vedolizumab (n = 14). Nine (15%) patients had recurrence of symptoms with a mean follow—up duration of 2 years. Conclusion: ICPIs might cause upper GI toxicity that is severe enough to require immunosuppression and hospitalization. Gastric involvement was evident more often than duodenal involvement on endoscopic and histological level. Patients without other risk factors for gastritis had isolated gastric involvement on endoscopy, although histologically duodenal inflammation was evident in 39%. Ulceration was more frequently found in isolated upper GI toxicities than concurrent upper and lower GI toxicities.1231_A Figure 1 No Caption available.1231_B Figure 2 No Caption available.1231_C Figure 3 No Caption available.