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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / chemically induced*
  • Cytokine Release Syndrome / drug therapy
  • Cytokine Release Syndrome / etiology*
  • Female
  • Humans
  • Immunotherapy, Adoptive / adverse effects*
  • Male
  • Middle Aged
  • Neoplasms / therapy
  • Receptors, Chimeric Antigen / therapeutic use*
  • Registries*
  • Retrospective Studies
  • Stroke Volume
  • Troponin / blood

Substances

  • Antibodies, Monoclonal, Humanized
  • Receptors, Chimeric Antigen
  • Troponin
  • tocilizumab