Back to Search Start Over

Cardiovascular Events Among Adults Treated With Chimeric Antigen Receptor T-Cells (CAR-T).

Authors :
Alvi RM
Frigault MJ
Fradley MG
Jain MD
Mahmood SS
Awadalla M
Lee DH
Zlotoff DA
Zhang L
Drobni ZD
Hassan MZO
Bassily E
Rhea I
Ismail-Khan R
Mulligan CP
Banerji D
Lazaryan A
Shah BD
Rokicki A
Raje N
Chavez JC
Abramson J
Locke FL
Neilan TG
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.)

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