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Meta-Analysis
. 2024 Oct 1;7(10):e2437222.
doi: 10.1001/jamanetworkopen.2024.37222.

Cardiovascular Events After Chimeric Antigen Receptor T-Cell Therapy for Advanced Hematologic Malignant Neoplasms: A Meta-Analysis

David Koeckerling  1   2 , Rohin K Reddy  3   4 , Joseph Barker  3 , Christian Eichhorn  5 , Pip Divall  6 , James P Howard  3 , Felix Korell  7 , Michael Schmitt  7 , Peter Dreger  7 , Norbert Frey  1   2 , Lorenz H Lehmann  1   2   8
Affiliations
Meta-Analysis

Cardiovascular Events After Chimeric Antigen Receptor T-Cell Therapy for Advanced Hematologic Malignant Neoplasms: A Meta-Analysis

David Koeckerling et al. JAMA Netw Open. .

Abstract

Importance: The frequency and clinical phenotypes of cardiotoxic events in chimeric antigen receptor (CAR) T-cell recipients remain poorly understood given that landmark approval trials typically exclude patients with high-risk cardiovascular profiles and data from nontrial settings are scarce.

Objective: To summarize the prevalence of adverse cardiovascular events among adults receiving CAR T-cell therapies for advanced hematologic malignant neoplasms.

Data sources: MEDLINE, Embase, Cochrane Library, and Google Scholar were systematically searched from database inception until February 26, 2024.

Study selection: Observational studies were included if they comprised adult CAR T-cell recipients with advanced hematologic malignant neoplasms and if they systematically evaluated cardiovascular complications.

Data extraction and synthesis: Extraction of prespecified parameters related to the patient population, study design, and clinical events was performed at the study level by 2 independent reviewers in accordance with the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. Meta-analysis of single proportions was conducted using random-effect models with Freeman-Tukey double arcsine transformations to calculate pooled prevalence estimates. Sensitivity analysis was performed using generalized linear mixed models with logit transformations.

Main outcomes and measures: Ventricular and supraventricular arrhythmias, heart failure events, reduction in left ventricular ejection fraction, myocardial infarction, and cardiovascular and all-cause mortality.

Results: Thirteen studies comprising 1528 CAR T-cell recipients (median [IQR] age, 61 [58.7-63.0] years; 1016 males [66%]; 80% patients with lymphoma) were included. The median (IQR) duration of follow-up was 487 (294-530) days. On random-effects meta-analysis, we observed a pooled prevalence of 0.66% (95% CI, 0.00%-2.28%) for ventricular arrhythmia, 7.79% (95% CI, 4.87%-11.27%) for supraventricular arrhythmia, 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 generated similar findings.

Conclusions and relevance: This meta-analysis found a low prevalence of ventricular arrhythmia, myocardial infarction, and cardiovascular death among CAR T-cell recipients over a short-term to midterm follow-up. Left ventricular dysfunction and supraventricular arrhythmia were the most commonly reported cardiovascular complications, suggesting that cardiovascular surveillance strategies should focus on decreases in ejection fraction and supraventricular arrhythmia.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Howard reported receiving grants from the British Heart Foundation during the conduct of the study. Dr Schmitt reported receiving educational support from Novartis, Bristol Myers Squibb, Kite-Gilead, and Johnson &Johnson during the conduct of the study; receiving personal fees from MSD and Laboratoires Pierre Fabre outside the submitted work; and being cofounder and shareholder of TolerogenixX Ltd outside the submitted work. Dr Frey reported receiving personal fees from Bayer, Boehringer Ingelheim, Novartis, and AstraZeneca outside the submitted work. Dr Lehmann reported receiving speaker’s honoraria from MSD, Novartis, Daiichi Sankyo, and AstraZeneca and personal fees from Servier Pharmaceuticals and AstraZeneca outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Pooled Prevalence of Ventricular Arrhythmia and Supraventricular Arrhythmia
Inverse-variance random-effects models with Freeman-Tukey double arcsine transformation were used. Error bars represent 95% CIs. Diamonds indicate the pooled prevalence estimate and its associated 95% CI. Size of the squares represents weight.
Figure 2.
Figure 2.. Pooled Prevalence of Reduction in Left Ventricular Dysfunction and Heart Failure Events
Inverse-variance random effect models with Freeman-Tukey double arcsine transformation were used. Error bars represent 95% CIs. Diamonds indicate the pooled prevalence estimate and its associated 95% CI. Size of the squares represents weight.
Figure 3.
Figure 3.. Pooled Prevalence of Myocardial Infarction
Inverse-variance random effect models with Freeman-Tukey double arcsine transformation were used. Error bars represent 95% CIs. Diamonds indicate the pooled prevalence estimate and its associated 95% CI. Size of the squares represents weight.
Figure 4.
Figure 4.. Pooled Prevalence of Cardiovascular Death
Inverse-variance random effect models with Freeman-Tukey double arcsine transformation were used. Error bars represent 95% CIs. Diamonds indicate the pooled prevalence estimate and its associated 95% CI. Size of the squares represents weight.
See this image and copyright information in PMC

Comment in

References

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