Immune-related adverse events during anticancer immunotherapy: Pathogenesis and management

Immunotherapy is one of the most recent systemic treatments to emerge for use in oncology, and is based on the blocking of inhibitory immune checkpoints to potentiate the immune response to cancer. The anti-cytotoxic T lymphocyte-associated antigen-4 antibody ipilimumab and anti-programmed cell death protein 1 antibodies, including nivolumab and pembrolizumab, are currently available and widely used, and other immune-inhibiting antibodies are now under intensive investigation. These antibodies have shown efficacy in a growing number of tumor types, following initial observations of their notable effects in melanoma treatment. Despite the efficacy of these antibodies, their novel mechanisms of action are also associated with a new class of side effects called immune-related adverse events (IRAEs). These side effects do not share a common pathophysiology with other anticancer treatments and, therefore, they often require specific therapies. When detected early and correctly treated, IRAEs are reversible; however, they can become severe and life-threatening if underestimated or inappropriately treated. This review aims to revisit the pathogenesis of IRAEs, with attention to gastrointestinal manifestations, since these are common and potentially dangerous complications of immunotherapy and represent a major cause of treatment discontinuation. Recommendations and guidelines for the management of IRAEs are also presented, in order to provide a clear and applicable algorithm for use by clinicians.