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Cardiovascular Events Among Adults Treated With Chimeric Antigen Receptor T-Cells (CAR-T).
- Source :
-
Journal of the American College of Cardiology [J Am Coll Cardiol] 2019 Dec 24; Vol. 74 (25), pp. 3099-3108. - Publication Year :
- 2019
-
Abstract
- Background: Chimeric antigen receptors redirect T cells (CAR-T) to target cancer cells. There are limited data characterizing cardiac toxicity and cardiovascular (CV) events among adults treated with CAR-T.<br />Objectives: The purpose of this study was to evaluate the possible cardiac toxicities of CAR-T.<br />Methods: The registry included 137 patients who received CAR-T. Covariates included the occurrence and grade of cytokine release syndrome (CRS) and the administration of tocilizumab for CRS. Cardiac toxicity was defined as a decrease in the left ventricular ejection fraction or an increase in serum troponin. Cardiovascular events were a composite of arrhythmias, decompensated heart failure, and CV death.<br />Results: The median age was 62 years (interquartile range [IQR]: 54 to 70 years), 67% were male, 88% had lymphoma, and 8% had myeloma. Approximately 50% were treated with commercial CAR-T (Yescarta or Kymriah), and the remainder received noncommercial products. CRS, occurring a median of 5 days (IQR: 2 to 7 days) after CAR-T, occurred in 59%, and 39% were grade ≥2. Tocilizumab was administered to 56 patients (41%) with CRS, at a median of 27 h (IQR: 16 to 48 h) after onset. An elevated troponin occurred in 29 of 53 tested patients (54%), and a decreased left ventricular ejection fraction in 8 of 29 (28%); each occurred only in patients with grade ≥2 CRS. There were 17 CV events (12%, 6 CV deaths, 6 decompensated heart failure, and 5 arrhythmias; median time to event of 21 days), all occurred with grade ≥2 CRS (31% patients with grade ≥2 CRS), and 95% of events occurred after an elevated troponin. The duration between CRS onset and tocilizumab administration was associated with CV events, where the risk increased 1.7-fold with each 12-h delay to tocilizumab.<br />Conclusions: Among adults, cardiac injury and CV events are common post-CAR-T. There was a graded relationship among CRS, elevated troponin, and CV events, and a shorter time from CRS onset to tocilizumab was associated with a lower rate of CV events.<br /> (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Aged
Antibodies, Monoclonal, Humanized therapeutic use
Cardiovascular Diseases blood
Cytokine Release Syndrome drug therapy
Female
Humans
Male
Middle Aged
Neoplasms therapy
Retrospective Studies
Stroke Volume
Troponin blood
Cardiovascular Diseases chemically induced
Cytokine Release Syndrome etiology
Immunotherapy, Adoptive adverse effects
Receptors, Chimeric Antigen therapeutic use
Registries
Subjects
Details
- Language :
- English
- ISSN :
- 1558-3597
- Volume :
- 74
- Issue :
- 25
- Database :
- MEDLINE
- Journal :
- Journal of the American College of Cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 31856966
- Full Text :
- https://doi.org/10.1016/j.jacc.2019.10.038