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

Abstract

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.

Keywords Immune checkpoint inhibitors, colorectal cancer, immune-related adverse event, colitis

Ann Gastroenterol 2025; 38 (1): 72-79