Gastrointestinal toxicity of immune checkpoint inhibitors: from mechanisms to management

Immune checkpoint inhibitor therapies are a novel group of monoclonal antibodies with proven effectiveness in a wide range of malignancies, including melanoma, renal cell carcinoma, non-small-cell lung cancer, urothelial carcinoma and Hodgkin lymphoma. Their use in a range of other indications, such as gastrointestinal and head and neck cancer, is currently under investigation. The number of agents included in this drug group is increasing, as is their use. Although they have the potential to improve the treatment of advanced malignancies, they are also associated with a substantial risk of immune-related adverse events. The incidence of gastrointestinal toxicity associated with their use is second only in frequency to dermatological toxicity. Thus, gastroenterologists can expect to be increasingly frequently consulted by oncologists as part of a multidisciplinary approach to managing toxicity. Here, we describe this novel group of agents and their mechanisms of action. We review the manifestations of gastrointestinal toxicity associated with their use so that it can be recognized early and diagnosed accurately. We also discuss the proposed mechanisms underlying this toxicity and describe an algorithmic and, wherever possible, evidence-based approach to its management.