https://doi.org/10.1007/s00392-024-02526-y
1Universitätsklinikum Heidelberg Klinik für Innere Med. III, Kardiologie, Angiologie u. Pneumologie Heidelberg, Deutschland; 2Imperial College London National Heart & Lung Institute London, Großbritannien; 3Universitätsspital Basel Klinik für Innere Medizin Basel, Schweiz; 4University of Leicester Leicester, Großbritannien; 5Deutsches Krebsforschungszentrum (DKFZ) Heidelberg, Deutschland
Background:
The frequency and clinical phenotypes of adverse cardiac events in CAR T-cell recipients remain poorly understood, since landmark approval trials typically excluded patients with high-risk cardiovascular profiles and studies performed in real-world settings with systematic assessment of cardiotoxicity are scarce.
Objective:
To summarize the prevalence of specific cardiovascular complications in adult patients receiving CAR T-cell products for advanced hematological malignancies.
Methods:
The electronic databases MEDLINE, Embase, Cochrane Library and Google Scholar were systematically searched by a clinical librarian from inception until 26th February 2024. Observational studies comprising adult CAR T-cell recipients with advanced hematological malignancies and systematically evaluating cardiovascular complications were included. Extraction of prespecified parameters related to the patient population, study design and clinical events was performed at the study level by two independent reviewers. Key outcomes were ventricular and supraventricular arrhythmias, heart-failure events, left ventricular dysfunction, myocardial infarction, cardiovascular and all-cause mortality. Meta-analysis of single proportions using random effect models with Freeman-Tukey double arcsine transformations was conducted to calculate pooled prevalence estimates. Sensitivity analysis was performed using generalized linear mixed models with logit transformations. Subgroup analysis was conducted with respect to prospective vs retrospective study design. This study was registered on PROSPERO (CRD42024496470).
Results:
Following screening of 776 abstracts, 13 studies comprising 1528 CAR T-cell recipients were included. Most patients received CAR T-cell therapy for lymphoma (80%, IQR 30-98%) and were pretreated with anthracyclines (85%; IQR 80-87%). The median duration of follow-up was 487 (IQR 294-530) days. On random-effects meta-analysis we observed a pooled prevalence of 0.66% (95%CI 0.00-2.28%) for ventricular arrhythmias, 7.79% (95%CI 4.87-11.27%) for supraventricular arrhythmias, 8.68% (95%CI 2.26-17.97%) for left ventricular dysfunction, 3.87% (95%CI 1.77-6.62%) for heart-failure events, 0.62% (95% CI 0.02-1.74%) for myocardial infarction, and 0.63% (95% CI 0.13-1.38%) for cardiovascular death. The pooled prevalence of all-cause mortality was 30.01% (95%CI 19.49-41.68%). Sensitivity analyses using generalized linear mixed models with logit transformations generated similar findings. On subgroup analysis of prospective studies, a pooled prevalence of 0.00% was observed for ventricular arrhythmias, myocardial infarction and cardiovascular death.
Conclusion:
In this meta-analysis of proportions a low prevalence of ventricular arrhythmias, myocardial infarction and cardiovascular death was observed among adult CAR T-cell recipients over short- to mid-term follow-up. Left ventricular dysfunction and supraventricular arrhythmias were the most commonly reported cardiovascular complications.