Cardiovascular Complications Associated With Novel Cancer Immunotherapies
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Immune therapies represent a quantum leap in the fight against cancer. Recently approved immune checkpoint inhibitors that target receptors involved in immune escape of cancer cells (including cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed cell death protein ligand-1 (PD-L1) are increasingly being used for therapeutic benefit in a number of cancers. The robust anti-cancer activity of these agents has been accompanied by the recognition of new adverse effects, often due to the over activation of immune system, that may limit their therapeutic benefit and adversely impact outcomes. Combination treatments in particular, such as approaches using two targeted immunotherapy agents, have higher risk of adverse effects. Our review focuses on the approved checkpoint inhibitor therapies and their potential for cardiovascular toxicity. While very few cases of autoimmune cardiotoxicity and myocarditis have been reported in clinical trials, severe, life-threatening episodes of heart failure and hemodynamic compromise associated with the use of immune checkpoint inhibitors have recently been reported in the literature. Early recognition, diagnosis, and management of autoimmune myocarditis represent an important clinical challenge with no current guidelines available for prevention, identification, and treatment of this serious condition. This area of cardio-oncology is evolving rapidly as more drugs in this class are being discovered and pending approval. There is a need for future studies focused on prospective identification of biomarkers and clinical standards for treatment and long-term follow-up of cardiovascular toxicity to successfully continue the treatment of cancer while preventing the adverse outcomes with novel immune therapies.
KeywordsCheckpoint inhibitor Cytotoxic T cell-associated antigen-4 Programmed cell death protein-1 Programmed cell death protein ligand-1 Autoimmune myocarditis Acute heart failure
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The authors declare that they have no conflicts of interest.
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This article does not contain any studies with human or animal subjects performed by any of the authors.
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- 8.Basch E, Reeve BB, Mitchell SA, Clauser SB, Minasian LM, Dueck AC, et al. Development of the National Cancer Institute’s patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE). J Natl Cancer Inst. 2014;106(9)Google Scholar
- 12.http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/125377s0000lbl.pdf. Accessed December 28, 2016.
- 13.https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125554lbl.pdf. Accessed December 28, 2016.
- 14.http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125514s012lbl.pdf. Accessed December 28, 2016.
- 15.http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761041lbl.pdf. Accessed December 28, 2016.
- 16.•• Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J, Xu Y, et al. Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med. 2016;375(18):1749–55. This is a case report of 2 immune myocarditis events with an important molecular analysis of immune cross-reactivity that may direct future efforts for improved prediction of riskCrossRefPubMedPubMedCentralGoogle Scholar
- 17.Behling J, Kaes J, Munzel T, Grabbe S, Loquai C. New-onset third-degree atrioventricular block because of autoimmune-induced myositis under treatment with anti-programmed cell death-1 (nivolumab) for metastatic melanoma. Melanoma Res. 2016 13Google Scholar