Key result
Early hs-TnT rise >35% after CAR T therapy linked to ~126% higher all-cause mortality.
Why the study?
Previous retrospective studies suggested potential CAR T cell cardiotoxicity, prompting prospective evaluation of cardiotoxicity and the predictive value of cardiac biomarkers and classical risk factors for cardiac events and all-cause mortality.
Do baseline echocardiographic parameters and cardiac biomarker kinetics predict all-cause mortality and cardiotoxicity in patients receiving CAR T cell therapy?
Cohort (n=137)
No
Do baseline echocardiographic parameters and cardiac biomarker kinetics predict all-cause mortality and cardiotoxicity in patients receiving CAR T cell therapy?
Hazard Ratio: 2.26 (95% CI 1–5.17)
p-value: p=0.049
Prospective monitoring reveals that early post-infusion troponin T elevation and baseline septal hypertrophy predict all-cause mortality in patients receiving CAR T cell therapy, highlighting the need for intensified cardio-oncological surveillance.
Background: Assessment of cardiovascular risk is critical for patients with cancer. Previous retrospective studies suggest potential cardiotoxicity of CAR T cell therapies. We aimed to prospectively assess cardiotoxicity and the predictive value of cardiac biomarkers and classical risk factors (age, cardiac function, diabetes, arterial hypertension, smoking) for cardiac events and all-cause mortality (ACM). Methods: In this prospective cohort study, all patients treated with CAR T cell constructs (axi-cel, tisa-cel, brexu-cel, ide-cel, or the 3rd generation CAR HD-CAR-1) from Oct 1, 2018, to Sept 30, 2022 at the University Hospital Heidelberg were included. Surveillance included cardiac assessment with biomarkers (high-sensitive Troponin T (hs-cTnT), N-terminal brain natriuretic peptide (NT-proBNP)), 12-lead-ECG, and 2D echocardiography. ACM was defined as the primary study endpoint, while cardiotoxicity, defined by clinical syndromes of heart failure or decline in ejection fraction, served as a secondary endpoint. Findings: ). None of the baseline characteristics was able to predict the incidence of cardiac events. Interpretation: Reduced pre-lymphodepletion ejection fraction and early post-infusion biomarker kinetics may be associated with increased ACM and cardiotoxicity events. These findings may help to identify patients who could benefit from intensified cardio-oncological surveillance.
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Korell et al. (2024) conducted a cohort in Hematological malignancies (n=137). High-sensitive troponin T (hs-cTnT) increase >35% post-infusion vs. hs-cTnT increase ≤35% or decrease was evaluated on All-cause mortality (ACM) (HR 2.26, 95% CI 1.00-5.17, p=0.049). In patients receiving CAR T cell therapy, an early post-infusion increase in high-sensitive troponin T of more than 35% was significantly associated with increased all-cause mortality (HR 2.26).
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