Cardiovascular events occurred in 12% of adults treated with CAR-T, and the risk increased 1.7-fold with each 12-hour delay in administering tocilizumab for cytokine release syndrome.
Cohort (n=137)
What is the incidence of and risk factors for cardiac toxicity and cardiovascular events in adults treated with CAR-T cells?
Cardiac injury and cardiovascular events are common following CAR-T therapy, are strongly associated with cytokine release syndrome, and may be mitigated by earlier administration of tocilizumab.
Effect estimate: 1.7-fold risk increase per 12-h delay to tocilizumab
Background: Chimeric antigen receptors redirect T-cells (CAR-T) to target cancer cells. There are limited data characterizing cardiac toxicity and cardiovascular events (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.
“We found that elevated levels of inflammation, specifically C-reactive protein (CRP) levels, were the strongest predictors of MACE. CRS and ICANS grades were also associated with MACE.”
Alvi et al. (2019) conducted a cohort in Cancer treated with CAR-T (n=137). Chimeric Antigen Receptor T-Cells (CAR-T) was evaluated on Cardiovascular events (composite of arrhythmias, decompensated heart failure, and CV death) (1.7-fold risk increase per 12-h delay to tocilizumab). Cardiovascular events occurred in 12% of adults treated with CAR-T, and the risk increased 1.7-fold with each 12-hour delay in administering tocilizumab for cytokine release syndrome.