Cardiovascular Effects of CAR T Cell Therapy

Lefebvre, Bénédicte; Kang, Yu; Smith, Amanda M.; Frey, Noelle V.; Carver, Joseph R.; Scherrer‐Crosbie, Marielle

doi:10.1016/j.jaccao.2020.04.012

Cited by 116 publications

(144 citation statements)

References 25 publications

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“…Available data on CD19-targeting CAR T cell therapies have found varying incidences of cardiotoxicity. In a 145 CAR T cell adult patient cohort, 31 patients experienced major adverse cardiovascular events (21%) with grade 3–4 CRS conferring greater risk [ 38 ••]. However, a cohort of 137 adult patients undergoing CAR T cell for diffuse large B cell lymphoma (DLBCL), including transformed follicular lymphoma and multiple myeloma, observed a lower incidence, with 17 cardiovascular events (12%), all of which coincided with grade ≥ 2 CRS, and included 6 cardiovascular deaths [ 39 ••].…”

Section: Chimeric Antigen Receptor T Cell Therapymentioning

confidence: 99%

“…The mechanisms of cardiotoxicity for CD19-targeting CAR-T cell therapies are thought to be primarily mediated by the systemic inflammation of CRS [ 41 ]. In retrospective analyses of patients receiving CAR-T therapy, the degree of CRS has been strongly associated with the development of adverse cardiovascular outcomes [ 38 ••, 39 ]. Upon recognition of the tumor antigen domain, the activated CAR-T cells release numerous cytokines including IFNγ, IL-1, IL-2RA, TNFα, and the most well-studied mediator, IL-6 [ 42 ].…”

Section: Chimeric Antigen Receptor T Cell Therapymentioning

confidence: 99%

“…Preexisting cardiomyopathy, past total body irradiation, and anthracycline dose were not associated with increased incidence of hypotension [ 40 , 50 ]. The development of high grade CRS after infusion is associated with higher incidence of adverse cardiovascular outcomes following CAR T cell infusion [ 38 ••, 39 ••].…”

Section: Chimeric Antigen Receptor T Cell Therapymentioning

confidence: 99%

See 2 more Smart Citations

Immunotherapy-Associated Cardiotoxicity of Immune Checkpoint Inhibitors and Chimeric Antigen Receptor T Cell Therapy: Diagnostic and Management Challenges and Strategies

et al. 2021

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Section: Chimeric Antigen Receptor T Cell Therapymentioning

confidence: 99%

Section: Chimeric Antigen Receptor T Cell Therapymentioning

confidence: 99%

Section: Chimeric Antigen Receptor T Cell Therapymentioning

confidence: 99%

See 1 more Smart Citation

Immunotherapy-Associated Cardiotoxicity of Immune Checkpoint Inhibitors and Chimeric Antigen Receptor T Cell Therapy: Diagnostic and Management Challenges and Strategies

et al. 2021

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“…Another single-center study of 145 patients reported that around 15% of patients developed clinical heart failure. However, the incidence of systolic dysfunction is not clear given only a small proportion of patients (17 of 145) had sequential echocardiogram available [ 43 ]. In our study of 187 patients undergoing CAR T cell therapy for refractory or relapsed, aggressive non-Hodgkin lymphoma, baseline echocardiogram was performed in all, and 116 patients with grade ≥ 2 CRS had follow-up echocardiogram.…”

Section: Chimeric Antigen Receptor T Cell Therapymentioning

confidence: 99%

“…Similarly, another single-center study did not find any influence of cancer subtype (CLL, ALL, and DLBCL) on the development of MACE. However, the study interestingly found that the higher baseline creatinine was associated with MACE following CAR T cell therapy [ 43 ].…”

Section: Chimeric Antigen Receptor T Cell Therapymentioning

confidence: 99%

Cardiotoxicity of Contemporary Anticancer Immunotherapy

Dalbo

Patel

Parikh

et al. 2020

Curr Treat Options Cardio Med

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Purpose of review Contemporary anticancer immunotherapy, particularly immune checkpoint inhibitors (ICI) and chimeric antigen receptor (CAR) T cell therapy, has changed the landscape of treatment for patients with a variety of malignancies who historically had a poor prognosis. However, both immune checkpoint inhibitors and CAR T cell therapy are associated with serious cardiovascular adverse effects. As immunotherapy evolves to include high-risk patients with preexisting cardiovascular risk factors and disease, the risk and relevance of its associated cardiotoxicity will be even higher. Recent findings ICI can cause myocarditis, which usually occurs early after initiation, can be fulminant, and prompt treatment with high-dose corticosteroids is crucial. CAR T cell therapy frequently leads to cytokine release syndrome, which is associated with cardiomyopathy or arrhythmia development and may also result in circulatory collapse. Supportive treatment, as well as tocilizumab, an anti-interleukin-6 receptor antibody, is the cornerstone of treatment. Recent findings suggest that preexisting cardiovascular risk factors and disease may increase the risk of such cardiotoxicity, and prompt recognition, as well as treatment, may favorably alter the outcomes. Summary ICI and CAR T cell therapy have improved cancer-related outcomes; however, they both are associated with potentially therapy-limiting cardiotoxicity. Cardio-oncologists are required to play an important role in patient selection, pretherapy cardiovascular optimization, and prompt recognition and treatment of cardiotoxicity.

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Cardiovascular Events After Chimeric Antigen Receptor T-Cell Therapy for Advanced Hematologic Malignant Neoplasms

Koeckerling,

Reddy,

Barker

et al. 2024

JAMA Netw Open

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ImportanceThe 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.ObjectiveTo summarize the prevalence of adverse cardiovascular events among adults receiving CAR T-cell therapies for advanced hematologic malignant neoplasms.Data SourcesMEDLINE, Embase, Cochrane Library, and Google Scholar were systematically searched from database inception until February 26, 2024.Study SelectionObservational 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 SynthesisExtraction 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 MeasuresVentricular and supraventricular arrhythmias, heart failure events, reduction in left ventricular ejection fraction, myocardial infarction, and cardiovascular and all-cause mortality.ResultsThirteen 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 RelevanceThis 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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Cardiovascular Effects of CAR T Cell Therapy

Cited by 116 publications

References 25 publications

Immunotherapy-Associated Cardiotoxicity of Immune Checkpoint Inhibitors and Chimeric Antigen Receptor T Cell Therapy: Diagnostic and Management Challenges and Strategies

Immunotherapy-Associated Cardiotoxicity of Immune Checkpoint Inhibitors and Chimeric Antigen Receptor T Cell Therapy: Diagnostic and Management Challenges and Strategies

Cardiotoxicity of Contemporary Anticancer Immunotherapy

Cardiovascular Events After Chimeric Antigen Receptor T-Cell Therapy for Advanced Hematologic Malignant Neoplasms

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