Immune checkpoint inhibitor-associated gastrointestinal adverse events in patients with colorectal cancer

Purpose: Immune checkpoint inhibitors (ICI) are currently employed for the management of microsatellite instability-high (MSI-H) tumors with success. While immune checkpoint inhibitor related colitis is a very frequent and a devastating immune related adverse event (irAE) with the use of these agents, the incidence and characteristics of this inflammatory toxicity in patients with MSI-H colorectal cancers has not been examined. We aimed to describe the characteristics and clinical profile of patients diagnosed with luminal gastrointestinal irAE in patients treated with ICI for colorectal cancer in a tertiary cancer care center. Methods: This is a retrospective analysis that included adult cancer patients diagnosed with colorectal cancer that received ICI between 6/1/2014 and 12/31/2022. We report data on those that developed colitis as an irAE up to 3 months after the last dose of ICI confirmed by laboratory and/or imaging report. We included patients’ demographic characteristics, oncologic profile and outcomes as well as clinical course, endoscopic features as well as treatment and outcomes in terms of luminal gastrointestinal irAEs. Results: Out of 474 patients with colorectal cancer on ICI in our study period, only 18 developed a gastrointestinal irAE with an incidence of 3.8%. Patients were primarily Caucasian (88.8%) males (61.1%) with a median age of 69.5 years. The majority of these patients received combination therapy with anti-PD-1/L1 and CTLA-4 (50%). 66.6 % received ICI for MSI-H colorectal cancer. 11.1% of our sample were noted to have a second cancer-melanoma. The majority of patients had grade 1-2 colitis (61.2%) and grade 1-2 diarrhea (88.8%). Only 5 patients underwent endoscopic evaluation of whom, 2 had ulcerative inflammation necessitating use of selective immunosuppressive therapy with biologics. 61.1% had to withhold cancer treatment due toxicity. With regards to other gastrointestinal irAEs among this population, 41.4% and 5.8% were noted to have liver and pancreas toxicity respectively, with a median CTCAE grade of severity 2. The majority of our cohort received steroids as therapy. Conclusion: Luminal gastrointestinal irAEs seem to occur less frequently and at a lower severity among patients with MSI-H colorectal cancer after checkpoint inhibitors exposure compared to the overall incidence of the same among other cancers reported in literature. Larger prospective studies are necessary to determine the role of tumor biology and the gut microbiome in the disease profile and severity of immune related adverse events of the GI organ system.