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

Background: Immune checkpoint inhibitors (ICI) target microsatellite instability-high (MSI-H) tumors with success. The incidence and characteristics of ICI-related colitis (IMC) in patients with MSI-H colorectal cancers (CRC) are unclear.

Methods: We performed a retrospective analysis of adult patients with CRC who received ICI between June 1, 2014, and December 31, 2022, including data on IMC observed up to 3 months after the last dose of ICI. Patients' demographics, oncologic profile, endoscopic features, treatment and clinical outcomes were evaluated.

Results: Of 474 patients with CRC receiving ICI during our study period, 18 developed IMC (3.8%). The majority were Caucasian (88.8%), male (61.1%), and their median age was 69.5 years. Of these patients, 50% received combination therapy with anti-PD-1/L1 and CTLA-4; 66.6% had MSI-H colorectal cancer, 11.1% had a second cancer-melanoma, while 61.2% and 66.7% had grade 1-2 colitis and diarrhea respectively. Endoscopic evaluation was used in 5 patients, of whom 2 had ulcerative inflammation necessitating selective immunosuppressive therapy with biologics. Therapy was withheld in 61.1% because of toxicity; 41.4% and 5.8% were noted to have median Common Terminology Criteria for Adverse Events grade 2 liver and pancreas toxicity respectively. The majority of our cohort received steroid therapy.

Conclusions: The lower severity of IMC, compared to toxicity in other ICI-treated cancers, may be influenced by the tumor microenvironment in MSI-H colorectal cancer after ICI exposure. Larger prospective studies are necessary to determine the role of tumor biology and the gut microbiome in the disease profile and severity of IMC.