Dataset Information

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

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.

SUBMITTER: Alvi RM

PROVIDER: S-EPMC6938409 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Alvi Raza M RM Frigault Matthew J MJ Fradley Michael G MG Jain Michael D MD Mahmood Syed S SS Awadalla Magid M Lee Dae Hyun DH Zlotoff Daniel A DA Zhang Lili L Drobni Zsofia D ZD Hassan Malek Z O MZO Bassily Emmanuel E Rhea Isaac I Ismail-Khan Roohi R Mulligan Connor P CP Banerji Dahlia D Lazaryan Aleksandr A Shah Bijal D BD Rokicki Adam A Raje Noopur N Chavez Julio C JC Abramson Jeremy J Locke Frederick L FL Neilan Tomas G TG

Journal of the American College of Cardiology 20191201 25

<h4>Background</h4>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.<h4>Objectives</h4>The purpose of this study was to evaluate the possible cardiac toxicities of CAR-T.<h4>Methods</h4>The registry included 137 patients who received CAR-T. Covariates included the occurrence and grade of cytokine release syndrome (CRS) and the administration of tocilizu ...[more]

PMID: 31856966

Similar Datasets

Project description:BackgroundPivotal trials of chimeric antigen receptor T-cell (CAR-T) have identified common toxicities but may have been underpowered to detect cardiovascular and pulmonary adverse events (CPAEs).ObjectivesThis study sought to investigate CPAEs associated with commercial CD19-directed CAR-T therapy.MethodsIn this retrospective, pharmacovigilance study, the authors used the Food and Drug Administration adverse event reporting system to identify CPAEs associated with axicabtagene-ciloleucel and tisagenlecleucel. The authors evaluated disproportionate reporting by the reporting odds ratio (ROR) and the lower bound of the information component 95% credibility interval (IC025 >0 is deemed significant). Significant associations were further adjusted to age and sex (adj.ROR).ResultsThe authors identified CAR-T reports of 2,657 patients, including 546 CPAEs (20.5%). CPAEs overlapped with cytokine release syndrome in 68.3% (373 of 546) of the reports. Compared with the full database, CAR-T was associated with overreporting of tachyarrhythmias (n = 74 [2.8%], adj.ROR = 2.78 [95% CI: 2.21-3.51]), cardiomyopathy (n = 69 [2.6%], adj.ROR = 3.51 [2.42-5.09]), pleural disorders (n = 46 [1.7%], adj.ROR = 3.91 [2.92-5.23]), and pericardial diseases (n = 11 [0.4%], adj.ROR = 2.26 [1.25-4.09], all IC025 >0). Venous thromboembolic events (VTEs) were associated only with axicabtagene-ciloleucel therapy (n = 28 [1.6%], adj.ROR = 1.80 [1.24-2.62], IC025 >0). Atrial fibrillation (n = 55) was the leading tachyarrhythmia, followed by ventricular arrhythmias (n = 14). Tachyarrhythmias and VTEs were reported more often following axicabtagene-ciloleucel than tisagenlecleucel in an age- and sex-adjusted model (adj.ROR = 1.82 [1.04-3.18] and adj.ROR = 2.86 [1.18-6.93], respectively). Finally, the fatality rate of CPAEs was 30.9%.ConclusionsIn this largest post-marketing study to date, the authors identified an association between CAR-T and various CPAEs, including tachyarrhythmias, cardiomyopathy, pericardial and pleural disorders, and VTEs. These findings should be considered in the multidisciplinary assessment for and monitoring of CAR-T therapy recipients.

Dataset Information

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

Background

Objectives

Methods

Results

Conclusions

Publications

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

Similar Datasets

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