title: Treatment of the Immune-Related Adverse Effects of Immune Checkpoint Inhibitors: A Review.
abstract: OBJECTIVE
  The development of immune checkpoint inhibitors targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death-1 (PD-1) has significantly improved the treatment of a variety of cancers and led to US Food and Drug Administration approvals for patients with a variety of malignant neoplasms. Immune checkpoint inhibitors enhance antitumor immunity by blocking negative regulators of T-cell function that exist both on immune cells and on tumor cells. Although these agents can lead to remarkable responses, their use can also be associated with unique immune-related adverse effects (irAEs).
  
  
  METHODS
  In general, use of PD-1 inhibitors such as nivolumab and pembrolizumab has a lower incidence of irAEs compared with those that block CTLA-4 such as ipilimumab. The combination of nivolumab and ipilimumab has a higher rate of irAEs than either approach as monotherapy. Consensus guidelines regarding the treatment of the most common irAEs including rash, colitis, hepatitis, endocrinopathies, and pneumonitis have been established. The mainstay of irAE treatment consists of immunosuppression with corticosteroids or other immunosuppressant agents such as infliximab; most irAEs will resolve with appropriate management.
  
  
  CONCLUSIONS
  The clinical use of immune checkpoint inhibitors is expanding rapidly. Oncology practitioners will therefore be required to recognize and manage irAEs in a growing patient population. Early recognition and treatment are essential to prevent patient morbidity and mortality, and adherence to established algorithms is recommended.
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York2Weill Cornell Medical College, New York, New York.
authors.forename: Claire F
authors.initials: CF
authors.lastname: Friedman
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York2Weill Cornell Medical College, New York, New York.
authors.forename: Tracy A
authors.initials: TA
authors.lastname: Proverbs-Singh
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York2Weill Cornell Medical College, New York, New York.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Postow
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy; D005076:Exanthema / Q000139:chemically induced / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000074324:Ipilimumab; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy
chemical_list: D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D000074324:Ipilimumab; C582435:pembrolizumab