Evaluation of all-cause mortality and cardiovascular safety in patients receiving chimeric antigen receptor T cell therapy: a prospective cohort study.

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

Overall, 137 patients (median age 60, range 20-83, IQR 16), were included in the study. 46 patients died during the follow up period (median 0.75 years, range 0.02-4.33, IQR 0.89) 57 month, with a median survival of 0.57 years (range 0.03-2.38 years, IQR 0.79). A septal wall thickness above 11 mm (HR 2.48, 95%-CI = 1.10-5.67,

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.

Funding

The German Center for Cardiovascular Research, German Research Foundation, and the Federal Ministry of Education and Research.

Informations de copyright

© 2024 The Author(s).

Déclaration de conflit d'intérêts

LHL: served on the advisory board for Daiichi Sankyio, Senaca, Astra Zeneca and Servier, as an external expert for Astra Zeneca and received speakers’ honoraria from Novartis and MSD. CMT: research support from Bayer AG. Advisory board member Pfizer, Janssen-Cilag GmbH. Grants and/or provision of investigational medicinal products from Pfizer, Daiichi Sankyo, BiolineRx. MS: research grants from Apogenix, Hexal and Novartis. Travel grants from Hexal and Kite. Financial support for educational activities and conferences from bluebird bio, Kite and Novartis. Advisory board member of MSD. (Co-)PI of clinical trials of MSD, GSK, Kite and BMS. Co-Founder and shareholder of TolerogenixX Ltd. Head of the Cell Therapy Working Group of the German Society of Hematology & Oncology (DGHO). PD: consultancy AbbVie, AstraZeneca, Gilead, Janssen, Novartis, Riemser, Roche; speakers bureau AbbVie, Gilead, Novartis, Riemser, Roche; research support from Neovii and Riemser. AS: Travel grants from Hexal and Jazz Pharmaceuticals. Research grant from Therakos/Mallinckrodt. Consultancy BMS, Janssen-Cilag. Co-founder, shareholder, and part-time employee of TolerogenixX GmBH. EG: Honoraria for lectures by Roche Diagnostics. Member of the ACVC Biomarker Consensus Group. NF: Speaker honoraria/consulting fees from AstraZeneca, Boehringer Ingelheim, Bayer AG/Vital, BMS, Daiichi Sankyo, Edwards Lifesciences, GSK, Novartis, Pfizer, Sciarc, Synlab. Speaker of the Academy of the German Cardiac Society (DGK). None of the mentioned sources supported the work described within this manuscript. The remaining authors have nothing to disclose.