Cardiovascular Toxicities Associated with Cancer Immunotherapies
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Purpose of review
We review the cardiovascular toxicities associated with cancer immune therapies and discuss the cardiac manifestations, potential mechanisms, and management strategies.
The recent advances in cancer immune therapy with immune checkpoint inhibitors and adoptive cell transfer have improved clinical outcomes in numerous cancers. The rising use of cancer immune therapy will lead to a higher incidence in immune-related adverse events. Recent studies have highlighted several reports of severe cases of acute cardiotoxic events with immune therapy including fulminant myocarditis. We believe that immune-mediated myocarditis is a driving mechanism behind these cardiovascular toxicities and requires vigilant screening and prompt management with corticosteroids and immune-modulating drugs, especially with combination immune therapies.
While the incidence of serious cardiovascular toxicities with immune therapy appears low, these can be life-threatening especially when manifesting as acute immune-mediated myocarditis. Further collaborative studies are needed to effectively identify, characterize, and manage these events.
KeywordsImmune therapy Checkpoint inhibitors PD-1 CTLA-4 Cardiovascular toxicities Myocarditis
Compliance with Ethical Standards
Conflict of Interest
Daniel Y. Wang, Gosife Donald Okoye, and Thomas G. Neilan declare that they have no conflict of interest.
Douglas B. Johnson reports being on the advisory board for BMS and Genoptix, and grants from Incyte.
Javid J. Moslehi reports personal fees from Pfizer, Novartis, Bristol-Myers Squibb, Takeda, Ariad, Vertex, Acceleron, Incyte, Verastem, RGenix, StemCentRx, Heat Biologics, and Pharmacyclics
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 7.Tadokoro T, Keshino E, Makiyama A, Sasaguri T, Ohshima K, Katano H, et al. Acute lymphocytic myocarditis with anti-PD-1 antibody nivolumab. Circ Heart Fail. 2016;9(10).Google Scholar
- 10.•• 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. Case report documenting fulminant myocarditis with combination ICI with histopathologic evidence of selective clonal T-cell populations within the myocardium, tumor and skeletal muscle.CrossRefPubMedGoogle Scholar
- 13.Coley WB. The treatment of malignant tumors by repeated inoculations of erysipelas. With a report of ten original cases. 1893. Clin Orthop Relat Res. 1991(262):3-11.Google Scholar
- 27.• Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, et al. Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy. N Engl J Med. 2016;375(19):1845–55. Phase 3 clinical trial with higher dose of ipilimumab with one reported case of myocarditis.CrossRefPubMedGoogle Scholar
- 28.• Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(1):23–34. Phase 3 clinical trial that led to the approval of the first combination immune therapy in cancer. One patient developed myocarditis in the single ipilimumab arm.CrossRefPubMedGoogle Scholar
- 40.Gibson R, Delaune J, Szady A, Markham M. Suspected autoimmune myocarditis and cardiac conduction abnormalities with nivolumab therapy for non-small cell lung cancer. BMJ Case Rep. 2016;2016.Google Scholar
- 50.Goff SL, Dudley ME, Citrin DE, Somerville RP, Wunderlich JR, Danforth DN, et al. Randomized, prospective evaluation comparing intensity of lymphodepletion before adoptive transfer of tumor-infiltrating lymphocytes for patients with metastatic melanoma. J Clin Oncol. 2016;34(20):2389–97.CrossRefPubMedGoogle Scholar