Treatment of the Immune-Related Adverse Effects of Immune Checkpoint Inhibitors: A Review

JAMA Oncol. 2016 Oct 1;2(10):1346-1353. doi: 10.1001/jamaoncol.2016.1051.


Importance: 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).

Observations: 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 and relevance: 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.

Publication types

  • Review

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antineoplastic Agents / adverse effects*
  • Chemical and Drug Induced Liver Injury / etiology
  • Colitis / chemically induced
  • Colitis / drug therapy
  • Exanthema / chemically induced
  • Exanthema / drug therapy
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Ipilimumab
  • Pneumonia / chemically induced
  • Pneumonia / drug therapy


  • Adrenal Cortex Hormones
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Immunosuppressive Agents
  • Ipilimumab
  • pembrolizumab