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  • Cardiovascular Events Among...
    Alvi, Raza M.; Frigault, Matthew J.; Fradley, Michael G.; Jain, Michael D.; Mahmood, Syed S.; Awadalla, Magid; Lee, Dae Hyun; Zlotoff, Daniel A.; Zhang, Lili; Drobni, Zsofia D.; Hassan, Malek Z.O.; Bassily, Emmanuel; Rhea, Isaac; Ismail-Khan, Roohi; Mulligan, Connor P.; Banerji, Dahlia; Lazaryan, Aleksandr; Shah, Bijal D.; Rokicki, Adam; Raje, Noopur; Chavez, Julio C.; Abramson, Jeremy; Locke, Frederick L.; Neilan, Tomas G.

    Journal of the American College of Cardiology, 12/2019, Letnik: 74, Številka: 25
    Journal Article

    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. The purpose of this study was to evaluate the possible cardiac toxicities of CAR-T. 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. 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. 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. Display omitted