Synapse - Biomarkers and cardiovascular outcomes in chimeric antigen receptor T-cell therapy recipients

Biomarkers and cardiovascular outcomes in chimeric antigen receptor T-cell therapy recipients Journal Article

Authors:	Mahmood, S. S.; Riedell, P. A.; Feldman, S.; George, G.; Sansoterra, S. A.; Althaus, T.; Rehman, M.; Mead, E.; Liu, J. E.; Devereux, R. B.; Weinsaft, J. W.; Kim, J.; Balkan, L.; Barbar, T.; Lee Chuy, K.; Harchandani, B.; Perales, M. A.; Geyer, M. B.; Park, J. H.; Lia Palomba, M.; Shouval, R.; Tomas, A. A.; Shah, G. L.; Yang, E. H.; Gaut, D. L.; Rothberg, M. V.; Horn, E. M.; Leonard, J. P.; Van Besien, K.; Frigault, M. J.; Chen, Z.; Mehrotra, B.; Neilan, T. G.; Steingart, R. M.
Article Title:	Biomarkers and cardiovascular outcomes in chimeric antigen receptor T-cell therapy recipients
Abstract:	Aims Chimeric antigen receptor T-cell therapy (CAR-T) harnesses a patient's immune system to target cancer. There are sparse existing data characterizing death outcomes after CAR-T-related cardiotoxicity. This study examines the association between CAR-T-related severe cardiovascular events (SCE) and mortality. Methods and results From a multi-centre registry of 202 patients receiving anti-CD19 CAR-T, covariates including standard baseline cardiovascular and cancer parameters and biomarkers were collected. Severe cardiovascular events were defined as a composite of heart failure, cardiogenic shock, or myocardial infarction. Thirty-three patients experienced SCE, and 108 patients died during a median follow-up of 297 (interquartile range 104-647) days. Those that did and did not die after CAR-T were similar in age, sex, and prior anthracycline use. Those who died had higher peak interleukin (IL)-6 and ferritin levels after CAR-T infusion, and those who experienced SCE had higher peak IL-6, C-reactive protein (CRP), ferritin, and troponin levels. The day-100 and 1-year Kaplan-Meier overall mortality estimates were 18% and 43%, respectively, while the non-relapse mortality (NRM) cumulative incidence rates were 3.5% and 6.7%, respectively. In a Cox model, SCE occurrence following CAR-T was independently associated with increased overall mortality risk [hazard ratio (HR) 2.8, 95% confidence interval (CI) 1.6-4.7] after adjusting for age, cancer type and burden, anthracycline use, cytokine release syndrome grade >= 2, pre-existing heart failure, hypertension, and African American ancestry; SCEs were independently associated with increased NRM (HR 3.5, 95% CI 1.4-8.8) after adjusting for cancer burden. Conclusion Chimeric antigen receptor T-cell therapy recipients who experience SCE have higher overall mortality and NRM and higher peak levels of IL-6, CRP, ferritin, and troponin.
Keywords:	mortality; cardiotoxicity; chimeric antigen receptor; cardiomyopathy; adults; troponin-i; myocarditis; cancer; cardiovascular events; cardio-oncology; car-t cells
Journal Title:	European Heart Journal
Volume:	44
Issue:	22
ISSN:	0195-668X
Publisher:	Oxford University Press
Date Published:	2023-06-07
Start Page:	2029
End Page:	2042
Language:	English
ACCESSION:	WOS:000953675900001
DOI:	10.1093/eurheartj/ehad117
PROVIDER:	wos
PMCID:	PMC10256191
PUBMED:	36939851
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding author is Syed Mahmood -- Source: Wos