Toxicities in Immune Checkpoint Inhibitors

Although cancer research has evolved, chemotherapy has been the backbone of systemic treatment. Over the last several years, the increasing availability of tumor mutation profiling has contributed to the use of molecular targeted therapy. Since ipilimumab was approved for advanced melanoma in 2011, immune checkpoint inhibitors (ICIs) such as inhibitors of programmed death protein 1, programmed death-ligand 1, and cytotoxic T-lymphocyte-associated protein 4 have expanded the horizon of cancer treatment for patients with advanced or refractory disease. One of the main reasons that ICIs are widely used is a relatively well-tolerated side effect profile compared with that of chemotherapy. Side effects of ICIs are usually reversible by corticosteroids or other immunosuppressants. However, ICIs can cause grade 3-4 adverse events, for which ICIs are discontinued. Adverse events range from generalized symptoms such as fatigue, pyrexia, nausea, or infusion reaction to inflammation of any organ systems mimicking autoimmune diseases. These immune-related adverse events (irAEs) include dermatitis, colitis, hepatitis, endocrinopathies including thyroid dysfunction, hypophysitis, adrenal insufficiency, and type 1 diabetes, pneumonitis, nephritis, pancreatitis, neurologic diseases, cardiotoxicity, ocular toxicity, hematologic toxicity, and rheumatologic toxicity. Clinicians may encounter challenging clinical scenarios in which ICIs may complicate treatment courses despite their use as last-line agents for refractory and metastatic diseases. Patients with a history of stem cell or organ transplantation, underlying autoimmune diseases, or preexisting infectious diseases or elderly patients having comorbidities present unique considerations before beginning ICI therapy. This chapter discusses ICI-induced irAEs, as well as the use of ICIs in challenging patient populations.