PMID- 32966880
OWN - NLM
STAT- MEDLINE
DCOM- 20210623
LR  - 20210623
IS  - 1523-6536 (Electronic)
IS  - 1083-8791 (Linking)
VI  - 26
IP  - 12
DP  - 2020 Dec
TI  - Cardiovascular Events Associated with Chimeric Antigen Receptor T Cell Therapy: 
      Cross-Sectional FDA Adverse Events Reporting System Analysis.
PG  - 2211-2216
LID - S1083-8791(20)30581-4 [pii]
LID - 10.1016/j.bbmt.2020.08.036 [doi]
AB  - Chimeric antigen receptor (CAR) T cell therapy is approved in the United States 
      for the treatment of acute lymphocytic leukemia and aggressive B cell lymphomas. 
      Multiple cardiovascular adverse events (CVEs) associated with CAR-Ts have been 
      observed in small studies, but no large-scale studies exist. Leveraging the Food 
      and Drug Administration (FDA) Adverse Events Reporting System (FAERS), we 
      identified all reported adverse events (AEs) associated with CAR-T therapy 
      (tisagenlecleucel and axicabtagene ciloleucel) from 2017 to 2019. Reports with 
      missing age and sex were excluded. CVEs were classified into arrhythmias, heart 
      failure (HF), myocardial infarction (MI), and other CVEs. Logistic regression and 
      hierarchical clustering were used to identify factors associated with CVEs. A 
      total of 996 reported AEs were observed (39.1% associated with tisagenlecleucel 
      and 60% with axicabtagene ciloleucel). Of all patients experiencing AEs, the 
      median age was 54 (interquartile range, 21 to 65) years; 38.9% were females. In 
      total, 19.7% (196) of all AEs reported to the FDA were CVEs. The most common CVEs 
      were arrhythmia (77.6%), followed by HF (14.3%) and MI (0.5%). In adjusted 
      analysis a positive association was observed between those presenting with CVE 
      with neurotoxicity (odds ratio, 1.76; 95% confidence interval, 1.20 to 2.60; 
      P = .004). Additionally, when both CVE and cytokine release syndrome (CRS) are 
      present, neurotoxicity is the most common noncardiac AE, which clusters with them 
      (Jaccard similarity: 73.1). The mortality rate was 21.1% overall but 30.1% for 
      those reporting CVEs. In FAERS, reported CVEs with CAR-T are associated with high 
      reported mortality. The development of either CRS or neurotoxicity should prompt 
      vigilance for cardiovascular events.
CI  - Copyright (c) 2020 American Society for Transplantation and Cellular Therapy. 
      Published by Elsevier Inc. All rights reserved.
FAU - Guha, Avirup
AU  - Guha A
AD  - Harrington Heart and Vascular Institute, University Hospitals, Case Western 
      Reserve University, Cleveland, Ohio.
FAU - Addison, Daniel
AU  - Addison D
AD  - Cardio-Oncology Program, Division of Cardiology, The Ohio State University 
      Medical Center, Columbus, Ohio; Division of Cancer Prevention and Control, 
      Department of Internal Medicine, College of Medicine, The Ohio State University, 
      Columbus, Ohio.
FAU - Jain, Prantesh
AU  - Jain P
AD  - Division of Hematology and Oncology, University Hospitals of Cleveland and Case 
      Western Reserve University, Cleveland, Ohio.
FAU - Gutierrez, Jahir M
AU  - Gutierrez JM
AD  - Layer6 Inc., Toronto, Ontario, Canada.
FAU - Ghosh, Arjun
AU  - Ghosh A
AD  - Cardio-Oncology Service, Bart's Heart Centre, St Bartholomew's Hospital, London, 
      United Kingdom; Cardio-Oncology Service, University College London Hospital, 
      Hatter Cardiovascular Institute, London, United Kingdom.
FAU - Roddie, Claire
AU  - Roddie C
AD  - Department of Hematology, University College London Hospital, London, United 
      Kingdom.
FAU - de Lima, Marcos
AU  - de Lima M
AD  - Division of Hematology and Oncology, University Hospitals of Cleveland and Case 
      Western Reserve University, Cleveland, Ohio.
FAU - Al-Kindi, Sadeer
AU  - Al-Kindi S
AD  - Harrington Heart and Vascular Institute, University Hospitals, Case Western 
      Reserve University, Cleveland, Ohio.
FAU - Oliveira, Guilherme H
AU  - Oliveira GH
AD  - Cardio-Oncology Program, Division of Cardiovascular Sciences, University of South 
      Florida, Tampa General Hospital and Moffitt Cancer Center, Tampa, Florida. 
      Electronic address: oliveirag@usf.edu.
LA  - eng
GR  - P30 CA016058/CA/NCI NIH HHS/United States
GR  - K12 CA133250/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20200920
PL  - United States
TA  - Biol Blood Marrow Transplant
JT  - Biology of blood and marrow transplantation : journal of the American Society for 
      Blood and Marrow Transplantation
JID - 9600628
RN  - 0 (Receptors, Chimeric Antigen)
SB  - IM
MH  - *Cardiovascular Diseases/etiology
MH  - Cell- and Tissue-Based Therapy
MH  - Cross-Sectional Studies
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Receptors, Chimeric Antigen
MH  - United States
MH  - United States Food and Drug Administration
OTO - NOTNLM
OT  - Cardio-oncology
OT  - Cardiovascular events
OT  - Chimeric antigen receptor T cells
OT  - FAERS
OT  - Hierarchical clustering
OT  - ICANS
EDAT- 2020/09/24 06:00
MHDA- 2021/06/24 06:00
CRDT- 2020/09/23 20:05
PHST- 2020/04/23 00:00 [received]
PHST- 2020/08/28 00:00 [revised]
PHST- 2020/08/31 00:00 [accepted]
PHST- 2020/09/24 06:00 [pubmed]
PHST- 2021/06/24 06:00 [medline]
PHST- 2020/09/23 20:05 [entrez]
AID - S1083-8791(20)30581-4 [pii]
AID - 10.1016/j.bbmt.2020.08.036 [doi]
PST - ppublish
SO  - Biol Blood Marrow Transplant. 2020 Dec;26(12):2211-2216. doi: 
      10.1016/j.bbmt.2020.08.036. Epub 2020 Sep 20.