Author + information
- Bénédicte Lefebvre, MDa@BenedicteLefeb1,
- Yu Kang, MD, PhDa,
- Amanda M. Smith, MAa,
- Noelle V. Frey, MDb,
- Joseph R. Carver, MDa,c and
- Marielle Scherrer-Crosbie, MD, PhDa,∗ (, )@mariellesc1
- aDivision of Cardiovascular Diseases, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
- bDivision of Hematology and Oncology Diseases, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
- cAbramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
- ↵∗Address for correspondence:
Dr. Marielle Scherrer-Crosbie, Division of Cardiovascular Diseases, Department of Medicine, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, Pennsylvania 19104.
Background Anti-CD19 chimeric antigen receptor (CAR) T cell therapy holds great promise in the treatment of patients with hematologic malignancies. A high occurrence of cardiac dysfunction has been noted in children treated with CAR T cell therapy.
Objectives The aim of this study was to define the occurrence of major adverse cardiovascular events (MACE) in adult patients treated with CAR T cell therapy and assess the relationships among clinical factors, echocardiographic parameters, laboratory values, and cardiovascular outcomes.
Methods Baseline clinical, laboratory, and echocardiographic parameters were collected in 145 adult patients undergoing CAR T cell therapy. MACE included cardiovascular death, symptomatic heart failure, acute coronary syndrome, ischemic stroke, and de novo cardiac arrhythmia. Baseline parameters associated with MACE were identified using Cox proportional cause-specific hazards regression analysis.
Results Thirty-one patients had MACE (41 events) at a median time of 11 days (interquartile range: 6 to 151 days) after CAR T cell infusion. The median follow-up period was 456 days (interquartile range: 128 to 1,214 days). Sixty-one patients died. Cytokine release syndrome (CRS) occurred 176 times in 104 patients; the median time to CRS was 6 days (interquartile range: 1 to 8 days). The Kaplan-Meier estimates for MACE and CRS at 30 days were 17% and 53%, respectively. The Kaplan-Meier estimates for survival at 1 year was 71%. Multivariable Cox proportional cause-specific hazards regression analysis determined that baseline creatinine and grade 3 or 4 CRS were independently associated with MACE.
Conclusions Patients treated with CAR T cell therapy are at an increased risk for MACE and may benefit from cardiovascular surveillance. Further large prospective studies are needed to confirm the incidence and risk factors predictive of MACE.
This study was funded through National Heart, Lung, and Blood Institute grant 1R01HL130539-01 (to Dr. Scherrer-Crosbie). The authors have reported that they have no relationships relevant to the contents of this paper to disclose. This study was partially presented as an oral presentation at the American Heart Association Scientific Meeting, November 2019, Philadelphia. James Fang, MD, served Guest Associate Editor for this paper. Anju Nohria, MD, served as Guest Editor-in-Chief for this paper.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: CardioOncology author instructions page.
- Received November 3, 2019.
- Revision received April 22, 2020.
- Accepted April 23, 2020.
- 2020 The Authors