Cardiovascular events among adults treated with chimeric antigen receptor T-cells (CAR-T)

RM Alvi, MJ Frigault, MG Fradley, MD Jain… - Journal of the American …, 2019 - jacc.org
RM Alvi, MJ Frigault, MG Fradley, MD Jain, SS Mahmood, M Awadalla, DH Lee, DA Zlotoff…
Journal of the American College of Cardiology, 2019jacc.org
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 …
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.
jacc.org
以上显示的是最相近的搜索结果。 查看全部搜索结果