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Myocarditis in Patients Treated With Immune Checkpoint Inhibitors.

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.

journal_name

J Am Coll Cardiol

journal_title

Journal of the American College of Cardiology

authors

Mahmood SS,Fradley MG,Cohen JV,Nohria A,Reynolds KL,Heinzerling LM,Sullivan RJ,Damrongwatanasuk R,Chen CL,Gupta D,Kirchberger MC,Awadalla M,Hassan MZO,Moslehi JJ,Shah SP,Ganatra S,Thavendiranathan P,Lawrence DP,Groark

doi

10.1016/j.jacc.2018.02.037

subject

Has Abstract

pub_date

2018-04-24 00:00:00

pages

1755-1764

issue

eissn

0735-1097

issn

1558-3597

pii

S0735-1097(18)33368-0

journal_volume

pub_type

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Myocarditis in Patients Treated With Immune Checkpoint Inhibitors.