What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Cancer (hematologic malignancies) (n=2059). Intervention: Chimeric antigen receptor T cell (CAR-T) therapy. Primary outcome: Overall incidence of cardiovascular events (25.6% pooled incidence, 95% CI 0.177-0.335).

November 9, 2022Open Access

Cardiovascular effects associated with chimeric antigen receptor T cell therapy in cancer patients: A meta-analysis

Key Result

CAR-T cell therapy in cancer patients was associated with a 25.6% pooled incidence of overall cardiovascular events, most commonly arrhythmias, cardiovascular dysfunction, and heart failure.

Study Design

Type

Meta-Analysis (n=2,059)

Structured PICO

Does CAR-T cell therapy cause cardiovascular toxicities in cancer patients?

Population

2,059 cancer patients treated with CAR-T cell therapy across 25 studies, evaluated for cardiovascular toxicities.

Intervention

Chimeric antigen receptor T cell (CAR-T cell) therapy (target antigens including CD19, BCMA, and others)

Outcome

Pooled incidence rates of all-cause mortality, overall cardiovascular (CV) events, CV events with cytokine release syndrome (CRS) grade ≥ 2, hypotension, arrhythmias, cardiovascular dysfunction, heart failure (HF), CV deaths, acute coronary syndrome (ACS), cardiomyopathy, cardiac arrest, and other CV events.safety

CAR-T cell therapy is associated with a significant incidence of cardiovascular toxicities, particularly arrhythmias, hypotension, and heart failure, emphasizing the need for cardiovascular monitoring in these patients.

Main Result

Effect estimate: 25.6% pooled incidence (95% CI 0.177-0.335)

Limitations

Relatively small sample size limiting precise estimation of clinical outcomes
Lack of subgroup analyses for age, ethnicity, cancer type, tumor site, and CAR-T cell dose
Inability to adjust for confounding risk factors such as prior exposure to cardiotoxins
Potential publication and language bias due to inclusion of only published English studies
Heterogeneity in follow-up times and definitions of cardiovascular toxicity across included studies

Abstract

Background: Although numerous studies confirmed the marked efficacy of chimeric antigen receptor T cells (CAR-T cells) in many hematologic malignancies, severe cardiovascular toxicities remain to be a major obstacle when incorporating this technology. Furthermore, previous individual investigations regarding the cardiovascular toxicities of CAR-T cell therapy also reported controversial conclusions. Therefore, a meta-analysis was performed to further evaluate the impacts of CAR-T cell therapy on cardiovascular toxicities. Methods: The PubMed, Embase, Web of Science, and ClinicalTrials.gov databases were searched for eligible studies up to April 2022. All analyses were carried out using the R 4.1.0 software. Results: Eventually, 25 related studies consisting of 2,059 patients were enrolled in the current meta-analysis. We discovered that the pooled incidence rate of the all-cause mortality rate was 14.1% and that the pooled incidence rates of overall cardiovascular (CV) events and CV events with cytokine release syndrome (CRS) grade ≥ 2 were 25.6% and 14.2%, respectively. The pooled incidence of hypotension was 28.6%. Further analysis showed that the incidence rates of arrhythmias, cardiovascular dysfunction, heart failure (HF), CV deaths, acute coronary syndrome (ACS), cardiomyopathy, cardiac arrest, and other CV events were 19.2%, 8.0%, 5.3%, 1.8%, 2.5%, 2.9%, 1.3%, and 1.9%, respectively. Conclusion: Cancer patients treated with CAR-T cell therapy were at risk for cardiovascular toxicities, of which the most common cardiovascular events were arrhythmias, cardiovascular dysfunction, and heart failure. These findings would contribute to achieving more rational and individualized use of CAR-T cells in clinical treatment.

Bookmark

View Full Paper