Myocarditis in patients treated with immune checkpoint inhibitors Journal Article
| Authors: | Mahmood, S. S.; Fradley, M. G.; Cohen, J. V.; Nohria, A.; Reynolds, K. L.; Heinzerling, L. M.; Sullivan, R. J.; Damrongwatanasuk, R.; Chen, C. L.; Gupta, D.; Kirchberger, M. C.; Awadalla, M.; Hassan, M. Z. O.; Moslehi, J. J.; Shah, S. P.; Ganatra, S.; Thavendiranathan, P.; Lawrence, D. P.; Groarke, J. D.; Neilan, T. G. |
| Article Title: | 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. © 2018 American College of Cardiology Foundation |
| Keywords: | controlled study; human tissue; aged; primary tumor; unclassified drug; human cell; major clinical study; hepatitis; side effect; drug megadose; antineoplastic agent; prospective study; ipilimumab; ticilimumab; low drug dose; prevalence; immunoglobulin; steroid; vasculotropin inhibitor; medical record review; retrospective study; high risk patient; pneumonia; acetylsalicylic acid; cardiovascular disease; cardiovascular risk; diabetes mellitus; colitis; methylprednisolone; dermatitis; immunomodulating agent; anthracycline derivative; beta adrenergic receptor blocking agent; calcium channel blocking agent; dipeptidyl carboxypeptidase inhibitor; hydroxymethylglutaryl coenzyme a reductase inhibitor; heart arrest; heart hemodynamics; thymocyte antibody; angiotensin receptor antagonist; hypophysitis; gastritis; heart ejection fraction; disease registry; infliximab; myocarditis; troponin t; mycophenolic acid; immune checkpoint inhibitor; cardiovascular mortality; nivolumab; human; male; female; priority journal; article; checkpoint inhibitor; pembrolizumab; cardio-oncology; durvalumab; complete heart block; atezolizumab; avelumab; major adverse cardiac event |
| Journal Title: | Journal of the American College of Cardiology |
| Volume: | 71 |
| Issue: | 16 |
| ISSN: | 0735-1097 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2018-04-24 |
| Start Page: | 1755 |
| End Page: | 1764 |
| Language: | English |
| DOI: | 10.1016/j.jacc.2018.02.037 |
| PROVIDER: | scopus |
| PUBMED: | 29567210 |
| PMCID: | PMC6196725 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 May 2018 -- Source: Scopus |
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