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

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 PalombaRoni 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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 From a multi-centre registry of 202 patients receiving anti-CD19 CAR-T, covariates including standard baseline cardiovas- and results cular 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.

Original languageEnglish
Pages (from-to)2029-2042
Number of pages14
JournalEuropean Heart Journal
Volume44
Issue number22
DOIs
StatePublished - 7 Jun 2023
Externally publishedYes

Keywords

  • CAR-T cells
  • Cancer
  • Cardio-oncology
  • Cardiovascular events
  • Chimeric antigen receptor
  • Mortality

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