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. 2019 Dec 24;74(25):3099-3108.
doi: 10.1016/j.jacc.2019.10.038.

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

Raza M Alvi  1 , Matthew J Frigault  2 , Michael G Fradley  3 , Michael D Jain  4 , Syed S Mahmood  5 , Magid Awadalla  1 , Dae Hyun Lee  3 , Daniel A Zlotoff  6 , Lili Zhang  1 , Zsofia D Drobni  1 , Malek Z O Hassan  1 , Emmanuel Bassily  3 , Isaac Rhea  3 , Roohi Ismail-Khan  3 , Connor P Mulligan  1 , Dahlia Banerji  1 , Aleksandr Lazaryan  7 , Bijal D Shah  7 , Adam Rokicki  1 , Noopur Raje  8 , Julio C Chavez  7 , Jeremy Abramson  8 , Frederick L Locke  4 , Tomas G Neilan  9
Affiliations

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

Raza M Alvi et al. J Am Coll Cardiol. .

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.

Objectives: The purpose of this study was to evaluate the possible cardiac toxicities of CAR-T.

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.

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.

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.

Keywords: cardiovascular events; chimeric antigen receptor T cells; cytokine release syndrome; tocilizumab; troponin.

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Figures

Figure 1:
Figure 1:. Results
Diagram showing the results of the study. CAR-T = Chimeric antigen receptor T-cells, CRS= cytokine release syndrome, LVEF= left ventricular ejection fraction, HF= heart failure.
Central Illustration:
Central Illustration:. Relationship between elevated troponin, CRS and tocilizumab with cardiovascular events.
Relationship of elevated troponin, CRS (Lee 2014 Criteria) and tocilizumab administration with cardiovascular events.
See this image and copyright information in PMC

Comment in

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