Myocarditis Induced by Immunotherapy: A Rare but Fatal Complication

P. M. Mulendele *

Department of Cardiology P37, Ibn Rochd University Hospital, Casablanca, Morocco.

M. Njie

Department of Cardiology P37, Ibn Rochd University Hospital, Casablanca, Morocco.

M. B. Charfo

Department of Cardiology P37, Ibn Rochd University Hospital, Casablanca, Morocco.

G. M. Lukifimpa

Hospital Centre of South Seine and Marne, NEMOURS, France.

M. S. Boutar

Department of Cardiology P37, Ibn Rochd University Hospital, Casablanca, Morocco.

B. E. Ovaga

Department of Cardiology P37, Ibn Rochd University Hospital, Casablanca, Morocco.

M. Haboub

Department of Cardiology P37, Ibn Rochd University Hospital, Casablanca, Morocco and Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco.

S. Arous

Department of Cardiology P37, Ibn Rochd University Hospital, Casablanca, Morocco and Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco.

M. G. Benouna

Department of Cardiology P37, Ibn Rochd University Hospital, Casablanca, Morocco and Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco.

A. Drighil

Department of Cardiology P37, Ibn Rochd University Hospital, Casablanca, Morocco and Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco.

L. Azzouzi

Department of Cardiology P37, Ibn Rochd University Hospital, Casablanca, Morocco and Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco.

R. Habbal

Department of Cardiology P37, Ibn Rochd University Hospital, Casablanca, Morocco and Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco.

*Author to whom correspondence should be addressed.


Abstract

The emergence of immunotherapy and the gradual expansion of its indications in oncology will require particular vigilance to detect and quickly take care of the potential cardiac toxicities. They have improved prognosis and survival, including patients with kidney, lung or skin cancers (melanoma) and certain lymphomas. The incidence of unwanted cardiac events under immunotherapy is rare, undoubtedly less than 1 % under Ipilimab, Pembrolizumab and Nivolumab. Cardiac toxicity can be induced by many drugs but this time we focused on myocarditis induced by immuno-modulators, which is a rare but very fatal complication and has 2 main parts: an illustration of a clinical case and a review of the literature comprising generality, pathophysiology, clinical manifestations, diagnostic strategy and therapeutic management based on the guidelines of the European Society of cardiology on cardio-oncology recently published in 2022. Corticosteroids are drugs effective in the treatment of cardiac toxicity induced by immunotherapy.

Keywords: Myocarditis, immune check point inhibitors, corticosteroids


How to Cite

Mulendele, P. M., Njie , M., Charfo , M. B., Lukifimpa , G. M., Boutar , M. S., Ovaga , B. E., Haboub , M., Arous , S., Benouna , M. G., Drighil , A., Azzouzi , L., & Habbal , R. (2023). Myocarditis Induced by Immunotherapy: A Rare but Fatal Complication. Cardiology and Angiology: An International Journal, 12(4), 201–212. https://doi.org/10.9734/ca/2023/v12i4360


References

Zimmer L, Goldinger SM, Hofmann L, Loquai C, Ugurel S, Thomas I, et al. Neurological, respiratory, musculoskeletal, cardiac and ocular side-effects of anti-PD-1 therapy. Eur J Cancer. 2016:60:210– 25.

Läubli H, Balmelli C, Bossard M, Pfister O, Glatz K, Zippelius A. Acute heart failure due to autoimmune myocarditis under pembrolizumab treatment for metastatic melanoma. J Immunother Cancer. 2015:21;3:11.

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:e003514.

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;375:1749–55.

Mahmood SS, Fradley MG, Cohen JV, Nohria A, Reynolds KL, Heinzerling LM, et al. Myocarditis in Patients Treated With Immune Checkpoint Inhibitors. J Am Coll Cardiol. 2018;71:1755-1764

Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2018;36: 1714- 1768.

Ferreira M, Pichon E, Carmier D, Bouquet E, Pageot C, Bejan-Angoulvant T et al. Coronary toxicities of anti-PD-1 and anti-PD-L1 immunotherapies: A case report and review of the literature and international registries. Target Oncol. 2018;13:509-515.

Escudier M, Cautela J, Malissen N, Ancedy Y, Orabona M, Pinto J, et al. Clinical Features, Management, and Outcomes of Immune Checkpoint Inhibitor-Related Cardiotoxicity. Circulation. 2017; 136:2085–7.

Douglas B Johnson, Caroline A Nebhan, Javid J Moslehi, Justin M Balko. Immune-checkpoint inhibitors: long-term implications of toxicity. Nature Reviews Clinical Oncology. 2022;19:254– 267.

Available:https://www.ncbi.nlm.nih.gov/books/NBK519842/figure/neuroendo_hypophysi.F4/

Michelle Graciotti, Crostaina Berti, Harm Antan Kloh, Lara Kadalaff. The era bioengineering. How will this affect the next generation of cancer immunotherapy. Journal of Translation of Medicine; 2017:.

DOI: 10.1186/s12967-017-1244-2.

Douglas B Johnson, et al. Fulminant Myocarditis with Combination Immune Checkpoint Blockade. N Engl J Med. 2016;375:1749-1755.

Dolladille C, Akroun J, Morice P-M, Dompmartin A, Ezine E, Sassier M, et al. Cardiovascular immunotoxicities associated with immune checkpoint inhibitors: A safety meta-analysis. Eur Heart J. 2021;42:4964–4977.

Zhang L, Reynolds KL, Lyon AR, Palaskas N, Neilan TG. The evolving immunotherapy landscape and the epidemiology, diagnosis, and management of cardiotoxicity: JACC: CardioOncology primer. JACC CardioOncology. 2021;3:35–47.

Lyon AR, et al. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO), and the International Cardio-Oncology Society (IC-OS). Eur Heart J; 2022.

Courand PY, Croisille P, Khouatra C, Cottin V, Kirkorian G, Bonnefoy E. Churg-Strauss syndrome presenting with acute myocarditis and cardiogenic shock. Heart Lung Circ. 2012;21:178–81.

Salem JE, Allenbach Y, Vozy A, Brechot N, Johnson DB, Moslehi JJ, Kerneis M. Abatacept for Severe Immune Checkpoint Inhibitor-Associated Myocarditis. N Engl J Med. 2019;380:2377-2379.

Haanen JB, Carbonnel F, Robert C, Kerr KM, Peters S, Larkin J, et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol Off J Eur Soc Med Oncol. 2017;28:119-142.

Wang DY, Okoye GD, Neilan TG, Johnson DB, Moslehi JJ. Cardiovascular Toxicities Associated with Cancer Immunotherapies. Curr Cardiol Rep. 2017;19:21.

Salem JE, Allenbach Y, Vozy A, Brechot N, Johnson DB, Moslehi JJ, Kerneis M. Abatacept for Severe Immune Checkpoint Inhibitor-Associated Myocarditis. N Engl J Med. 2019;380:2377-2379.

Caforio ALP, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: A position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2013;3 :2636–2648.