Cardiovascular complications of immune checkpoint inhibitors
A. A. Kulievа,
E. I. Emelina,
G. E. Gendlin,
I. G. Nikitin,
S. K. Zyryanov,
S. I. Varentsov,
I. I. Zakharova Abstract
Cardiovascular toxicity of cancer therapies remains an urgent problem today. The creation of highly effect antitumor drugs also means the appearance of new adverse effects. Immune checkpoint inhibitors (ICI) is a new class of antitumor drugs that is different from traditional chemotherapeutic and targeted drugs. Immunotherapy with ICI (monoclonal antibodies targeting the cytotoxic T-lymphocyte associated antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1) or its ligand (PD-L1)) significantly improved the results of treatment of cancer therapy. These drugs regulate antitumor immunity and promote cancer regression and improve survival, but can also cause a wide range of immunity-related adverse events (AEs). Although cardiotoxicity associated with ICI is rare, it is important because of its high mortality rates. In recent years, cases of myocarditis and fatal heart failure have been recorded more often in patients receiving ICI. This review focuses on the mechanisms of cardiotoxicity, methods for the prevention and treatment of these adverse events. Severe cardiovascular consequences associated with the use of ICI are important issues for oncologists, cardiologists and immunologists.
About the Authors
A. A. Kulievа
Pirogov Russian National Research Medical University
Russian Federation
Russian Federation
Kulieva Aygyun - graduate student of the Department of hospital therapy №2, Faculty of Medicine
Moscow
E. I. Emelina
Pirogov Russian National Research Medical University
Russian Federation
Russian Federation
Emelina Elena - PhD, associate professor, Department of hospital therapy №2, Faculty of Medicine
Moscow
G. E. Gendlin
Pirogov Russian National Research Medical University
Russian Federation
Russian Federation
Gendlin Gennady - DM, professor, Department of hospital therapy №2, Faculty of Medicine
Moscow
I. G. Nikitin
Pirogov Russian National Research Medical University
Russian Federation
Russian Federation
Nikitin Igor - DM, professor, Head of Department of hospital therapy №2, Faculty of Medicine
Moscow
S. K. Zyryanov
Russian University of Nations’ Friendship; City Clinical Hospital №24
Russian Federation
Russian Federation
Zyryanov Sergey - MD, professor, Head of Department of General and Clinical Pharmacology, Medical Institute of the Peoples’ Friendship University of Russia; State Budgetary Institution of the City of Moscow City Clinical Hospital No. 24 of the Moscow City Health Department Russian Federation. SPIN code: 2725-9981
Moscow
S. I. Varentsov
City Clinical Hospital №24
Russian Federation
Russian Federation
Varentsov Sergey - anaesthesiologist-resuscitator, Head of Resuscitation Department
Moscow
I. I. Zakharova
City Clinical Hospital №24
Russian Federation
Russian Federation
Zakharova Irina - Cardiologist, Head of Cardiology Department
Moscow
References
1. Cheng H, Force T. Molecular mechanisms of cardiovascular toxicity of targeted cancer therapeutics. Circ Res. 2010;106(1):21— 34.
2. Moslehi JJ. Cardiovascular toxic effects of targeted cancer therapies. N Engl J Med. 2016;375(15):1457—1467.
3. Curigliano G, Cardinale D, Dent S, et al. Cardiotoxicity of anticancer treatments: Epidemiology, detection, and management. CA: A Cancer Journal for Clinicians. 2016;66(4):309—325. DOI:10.3322/caac.21341
4. Nelson MH, Paulos CM. Novel immunotherapies for hematologic malignancies. Immunol Rev. 2015 Jan;263(1):90-105. DOI: 10.1111/imr.12245
5. Schadendorf D, van Akkooi ACJ, Berking C, et al. Melanoma. Lancet. 2018 Sep 15;392(10151):971-984. DOI: 10.1016/S0140-6736(18)31559-9
6. Nasonov EL. Immune checkpoint inhibition and autoimmunity: rheumatological problems. Immune checkpoint inhibition and autoimmunity: rheumatological problems. Nauchnoprakticheskaya revmatologiya. 2018;56(1):5-9. (In Russ). DOI: 10.14412/19954484-2018-5-9
7. Chen L, Flies DB. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol. 2013;13:227-42. DOI: 10.1038/nri3405
8. Jain V, Bahia J, Mohebtash M, Barac A. Cardiovascular complications associated with novel cancer immunotherapies. Curr Treat Options Cardiovasc Med. 2017 May;19(5):36. DOI: 10.1007/s11936-017-0532-8
9. Atallah-Yunes SA, Kadado AJ, Kaufman GP, et al. Immune checkpoint inhibitor therapy and myocarditis: a systematic review of reported cases. J Cancer Res Clin Oncol. 2019;145:1527-1557. https://doi.org/10.1007/s00432019-02927-x
10. U.S. Department of Health and Human Services National Cancer Institute, Common terminology criteria for adverse events (CTCAE) version 5.0, https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm#ctc_50. Accessed date: 1 July 2019.
11. Norwood TG, Westbrook BC, Johnson DB, et al. Smoldering myocarditis following immune checkpoint blockade. J Immunother Cancer. 2017 Nov 21;5(1):91. DOI: 10.1186/s40425-017-0296-4
12. Bajwa R, Cheema A, Khan T, et al. Adverse Effects of Immune Checkpoint Inhibitors (Programmed Death-1 Inhibitors and Cytotoxic T-LymphocyteAssociated Protein-4 Inhibitors): Results of a Retrospective Study. Journal of Clinical Medicine Research. 2019;11(4):225—236. DOI:10.14740/jocmr3750
13. Varricchi G, Galdiero MR, Marone G, et al. Cardiotoxicity of immune checkpoint inhibitors. ESMO Open. 2017;2:e000247. DOI:10.1136/esmoopen-2017-000247
14. Mahmood SS, Fradley MG, Cohen JV, et al. Myocarditis in patients treated with immune checkpoint inhibitors. J Am Coll Cardiol. 2018 Apr 24;71(16):1755-1764. DOI: 10.1016/j.jacc.2018.02.037
15. Michel L, Rassaf T, Totzeck M. Cardiotoxicity from immune checkpoint inhibitors. Int J Cardiol Heart Vasc. 2019 Sep 7;25:100420. DOI: 10.1016/j.ijcha.2019.100420
16. Ganatra S, Neilan TG. Immune checkpoint inhibitor associated myocarditis. Oncologist. 2018 Aug;23(8):879-886. DOI: 10.1634/theoncologist.2018-0130
17. Frigeri M, Meyer P, Banfi C, et al. Immune checkpoint inhibitorassociated myocarditis: a new challenge for cardiologists. Can J Cardiol. 2018 Jan;34(1):92.e1-92.e3. DOI: 10.1016/j.cjca.2017.09.025
18. Roth ME, Muluneh B, Jensen BC, et al. Left ventricular dysfunction after treatment with ipilimumab for metastatic melanoma. Am J Ther. 2016;23:e1925—8
19. Yun S, Vincelette ND, Mansour I, et al. Late onset ipilimumab induced pericarditis and pericardial effusion: a rare but life threatening complication. Case Rep Oncol Med. 2015;2015:1—5. DOI: 10.1155/2015/794842
20. Lyon AR, Yousaf N, Battisti NML, Moslehi J, Larkin J. Immune checkpoint inhibitors and cardiovascular toxicity. Lancet Oncol. 2018 Sep;19(9):e447-e458. DOI: 10.1016/S1470-2045(18)30457-1
21. Voskens CJ, Goldinger SM, Loquai C, et al. The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network. PLoS One. 2013;8:e53745
22. Villadolid J, Amin A. Immune check point inhibitors in clinical practice: update on management of immunerelated toxicities. Transl Lung Cancer Res. 2015;4(5):560—75.
23. Jain V, Mohebtash M, Rodrigo ME, et al. Autoimmune myocarditis caused by immune checkpoint inhibitors treated with antithymocyte globulin. J Immunother. 2018 09;41(7):332-335.
24. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation 136.
25. Avxentyev NA, Frolov MYu, Makarov AS. Pharmacoeconomic study of Pembrolizumab and Nivolumab in the second line of therapy of advanced non-small cell lung cancer. Effektivnaya farmakoterapiya. 2019;15(24):38—24. (In Russ). DOI: 10.33978/2307-3586-2019-15-24-38-46
Review
For citations:
Kulievа A.A., Emelina E.I., Gendlin G.E., Nikitin I.G., Zyryanov S.K., Varentsov S.I., Zakharova I.I. Cardiovascular complications of immune checkpoint inhibitors. Kachestvennaya Klinicheskaya Praktika = Good Clinical Practice. 2019;(4):55-65. (In Russ.)
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