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A Review of Cancer Immunotherapy Toxicity: Immune Checkpoint Inhibitors
Neeraj Chhabra1,2, Joseph Kennedy3,4
1Cook County Health, Department of Emergency Medicine, Division of Medical Toxicology, 1950 W Polk Street, 7th Floor, Chicago, IL, 60612, USA. NChhabra@cookcountyhhs.org.
Cancer immunotherapy, which leverages features of the immune system to target neoplastic cells, has revolutionized the treatment of cancer. The use of these therapies has rapidly expanded in the past two decades. Immune checkpoint inhibitors represent one drug class within immunotherapy with its first agent FDA-approved in 2011. Immune checkpoint inhibitors act by disrupting inhibitory signals from neoplastic cells to immune effector cells, allowing activated T-cells to target these neoplastic cells. Unique adverse effects associated with immune checkpoint inhibitors are termed immune-related adverse effects (irAEs) and are usually immunostimulatory in nature. Almost all organ systems may be affected by irAEs including the dermatologic, gastrointestinal, pulmonary, endocrine, and cardiovascular systems. These effects range from mild to life-threatening, and their onset can be delayed several weeks or months. For mild irAEs, symptomatic care is usually sufficient. For higher grade irAEs, discontinuation of therapy and initiation of immunosuppressive therapy may be necessary. The management of patients with irAEs involves multidisciplinary care coordination with respect to the long-term goals the individual patient. Clinicians must be aware of the unique and sometimes fatal toxicologic profiles associated with immunotherapies to ensure prompt diagnosis and appropriate management.
Cancer immunotherapy, which leverages features of the immune system to target neoplastic cells, has revolutionized the treatment of cancer. The use of these therapies has rapidly expanded in the past two decades. Immune checkpoint inhibitors represent one drug class within immunotherapy with its first agent FDA-approved in 2011. Immune checkpoint inhibitors act by disrupting inhibitory signals from neoplastic cells to immune effector cells, allowing activated T-cells to target these neoplastic cells. Unique adverse effects associated with immune checkpoint inhibitors are termed immune-related adverse effects (irAEs) and are usually immunostimulatory in nature. Almost all organ systems may be affected by irAEs including the dermatologic, gastrointestinal, pulmonary, endocrine, and cardiovascular systems. These effects range from mild to life-threatening, and their onset can be delayed several weeks or months. For mild irAEs, symptomatic care is usually sufficient. For higher grade irAEs, discontinuation of therapy and initiation of immunosuppressive therapy may be necessary. The management of patients with irAEs involves multidisciplinary care coordination with respect to the long-term goals the individual patient. Clinicians must be aware of the unique and sometimes fatal toxicologic profiles associated with immunotherapies to ensure prompt diagnosis and appropriate management.
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