Immune checkpoint inhibitor-mediated colitis in gastrointestinal malignancies and inflammatory bowel disease

Abstract

Immune checkpoint inhibitors (ICI) have markedly changed the landscape of cancer therapy. By re-invigorating the immune system against tumors, ICI provide novel therapeutic options for a broad variety of malignancies, including many gastrointestinal (GI) cancers. However, these therapies can also induce autoimmune-like side effects in healthy tissue across the body. One of the most common of these side effects is ICI-mediated colitis and diarrhea (IMC). Here, we review the incidence and risk of IMC in ICI therapy, with a focus on what is known regarding IMC in patients with GI malignancies. We also discuss data available on the use of ICI and risk of IMC in patients with pre-existing inflammatory bowel disease, as these patients may have increased risk of IMC due to their underlying intestinal pathology.

Keywords: Immune checkpoint inhibitors; Cytotoxic T-lymphocyte antigen 4; Programmed cell death protein-1; Inflammatory bowel disease; Gastrointestinal cancer

Core Tip: Immune checkpoint inhibitor-mediated colitis and diarrhea (IMC) is a common immune-related adverse event with immune checkpoint inhibitor (ICI) therapy. The risk of IMC is most strongly associated with type of ICI used, but race, malignancy, and vitamin D use may also contribute to the risk of developing IMC. IMC incidence in gastrointestinal cancers appears comparable to other malignancies, but this is hampered by lack of a consistent definition for IMC and confounding by contemporaneous chemotherapy. Although patients with inflammatory bowel disease (IBD) are often excluded from treatment with ICI, available data suggest that they have increased risk of diarrhea and/or colitis compared to patients without IBD.