Myocarditis in Patients Treated With Immune Checkpoint Inhibitors

Mahmood SS, Fradley MG, Cohen JV, Nohria A, Reynolds KL, Heinzerling L, Sullivan RJ, Damrongwatanasuk R, Chen CL, Gupta D, Kirchberger MC, Awadalla M, Hassan MZO, Moslehi JJ, Shah SP, Ganatra S, Thavendiranathan P, Lawrence DP, Groarke JD, Neilan TG (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Journal of the American College of Cardiology Elsevier

Book Volume: 71

Pages Range: 1755-1764

Journal Issue: 16

DOI: 10.1016/j.jacc.2018.02.037

Abstract

BACKGROUND: Myocarditis is an uncommon, but potentially fatal, toxicity of immune checkpoint inhibitors (ICI). Myocarditis after ICI has not been well characterized. OBJECTIVES: The authors sought to understand the presentation and clinical course of ICI-associated myocarditis. METHODS: After observation of sporadic ICI-associated myocarditis cases, the authors created a multicenter registry with 8 sites. From November 2013 to July 2017, there were 35 patients with ICI-associated myocarditis, who were compared to a random sample of 105 ICI-treated patients without myocarditis. Covariates of interest were extracted from medical records including the occurrence of major adverse cardiac events (MACE), defined as the composite of cardiovascular death, cardiogenic shock, cardiac arrest, and hemodynamically significant complete heart block. RESULTS: The prevalence of myocarditis was 1.14% with a median time of onset of 34 days after starting ICI (interquartile range: 21 to 75 days). Cases were 65 ± 13 years of age, 29% were female, and 54% had no other immune-related side effects. Relative to controls, combination ICI (34% vs. 2%; p < 0.001) and diabetes (34% vs. 13%; p = 0.01) were more common in cases. Over 102 days (interquartile range: 62 to 214 days) of median follow-up, 16 (46%) developed MACE; 38% of MACE occurred with normal ejection fraction. There was a 4-fold increased risk of MACE with troponin T of ≥1.5 ng/ml (hazard ratio: 4.0; 95% confidence interval: 1.5 to 10.9; p = 0.003). Steroids were administered in 89%, and lower steroids doses were associated with higher residual troponin and higher MACE rates. CONCLUSIONS: Myocarditis after ICI therapy may be more common than appreciated, occurs early after starting treatment, has a malignant course, and responds to higher steroid doses.

Authors with CRIS profile

Lucie Heinzerling Department of Dermatology

Involved external institutions

H. Lee Moffitt Cancer Center & Research Institute US United States (USA) (US) Massachusetts General Hospital US United States (USA) (US) Brigham and Women's Hospital (BWH) US United States (USA) (US) Vanderbilt University US United States (USA) (US) Lahey Hospital & Medical Center US United States (USA) (US) Cornell University US United States (USA) (US) University of Toronto CA Canada (CA) New York Presbyterian Hospital US United States (USA) (US)

How to cite

APA:

Mahmood, S.S., Fradley, M.G., Cohen, J.V., Nohria, A., Reynolds, K.L., Heinzerling, L.,... Neilan, T.G. (2018). Myocarditis in Patients Treated With Immune Checkpoint Inhibitors. Journal of the American College of Cardiology, 71(16), 1755-1764. https://doi.org/10.1016/j.jacc.2018.02.037

MLA:

Mahmood, Syed S., et al. "Myocarditis in Patients Treated With Immune Checkpoint Inhibitors." Journal of the American College of Cardiology 71.16 (2018): 1755-1764.

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