Key result
Each 12-hour tocilizumab delay during CAR-T therapy linked to ~70% higher cardiovascular event risk.
Why the study?
There were limited data characterizing cardiac toxicity and cardiovascular events among adults treated with CAR-T.
What is the incidence of and risk factors for cardiac toxicity and cardiovascular events in adults treated with CAR-T cells?
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.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“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.”
“In this prospective study of patients receiving CAR T-cell therapy under strict cardiovascular surveillance, the incidence of MACE was <5%, and MACE occurred in patients with CRS within 7 days of therapy. The comparison with the higher occurrence of MACE in earlier retrospective studies with higher rates of CRS supports that earlier intervention, aggressive treatment, and close follow-up during CRS events are essential.”
May support earlier tocilizumab in grade 2 CRS to lower CV events after CAR-T; leaves open randomized confirmation.
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.
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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.
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