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

Autor: Syed S Mahmood, Peter A Riedell, Stephanie Feldman, Gina George, Stephen A Sansoterra, Thomas Althaus, Mahin Rehman, Elena Mead, Jennifer E Liu, Richard B Devereux, Jonathan W Weinsaft, Jiwon Kim, Lauren Balkan, Tarek Barbar, Katherine Lee Chuy, Bhisham Harchandani, Miguel-Angel Perales, Mark B Geyer, Jae H Park, M Lia Palomba, Roni Shouval, Ana A Tomas, Gunjan L Shah, Eric H Yang, Daria L Gaut, Michael V Rothberg, Evelyn M Horn, John P Leonard, Koen Van Besien, Matthew J Frigault, Zhengming Chen, Bhoomi Mehrotra, Tomas G Neilan, Richard M Steingart
Rok vydání: 2023
Předmět:
Zdroj: European Heart Journal.
ISSN: 1522-9645
0195-668X
DOI: 10.1093/eurheartj/ehad117
Popis: 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.
Databáze: OpenAIRE
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