Immune checkpoint inhibitor-induced colitis: A comprehensive review

Abstract

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target down-regulators of the anti-cancer immune response: Cytotoxic T-lymphocyte antigen-4, programmed cell death protein-1, and its ligand programmed death-ligand 1. ICIs have revolutionized the treatment of a variety of malignancies. However, many immune-related adverse events have also been described which mainly occurs as the immune system becomes less suppressed, affecting various organs including the gastrointestinal tract and causing diarrhea and colitis. The incidence of immune-mediated colitis (IMC) ranges from 1%-25% depending on the type of ICI and if used in combination. Endoscopically and histologically there is a significant overlap between IMC and inflammatory bowel disease, however more neutrophilic inflammation without chronic inflammation is usually present in IMC. Corticosteroids are recommended for grade 2 or more severe colitis while holding the immunotherapy. About one third to two thirds of patients are steroid refractory and benefit from infliximab. Recently vedolizumab has been found to be efficacious in steroid and infliximab refractory cases. While in grade 4 colitis, the immunotherapy is permanently discontinued, the decision is controversial in grade 3 colitis.

Keywords: Cytotoxic T-lymphocyte-associated antigen 4; Immune checkpoint inhibitors; Immune-mediated colitis; Immune-related adverse events; Programmed cell death protein 1; Programmed death-ligand 1.

Figure 1

Patient who experienced immune-mediated colitis 4 wk after ipilimumab therapy. Colonoscopy showed a sigmoid colon with ulcers, diffuse erythema, and loss of vascularity.