Cardiovascular Events Among Adults Treated With Chimeric Antigen Receptor T-Cells (CAR-T)

Alvi, Raza M.; Frigault, Matthew J.; Fradley, Michael G.; Jain, Michael D.; Mahmood, Syed; Awadalla, Magid; Lee, Dae Hyun; Zlotoff, Daniel A.; Zhang, Lili; Drobni, Zsófia; Hassan, M; Bassily, Emmanuel; Rhea, Isaac; Ismail‐Khan, Roohi; Mulligan, Connor P.; Banerji, Dahlia; Lazaryan, Aleksandr; Shah, Bijal; Rokicki, Adam; Raje, Noopur; Chávez, Julio C.; Abramson, Jeremy S.; Locke, Frederick L.; Neilan, Tomas G.

doi:10.1016/j.jacc.2019.10.038

Cited by 233 publications

(276 citation statements)

References 34 publications

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“…This systemic release of cytokines, characterized by increased IL-2, IL-6, IL-10, GCSF, IFN-γ, MCP-1, MIP-1-α, and TNF-α, likely contributes to cardiac injury in a situation analogous to cardiotoxicity in the setting of chimeric antigen receptor (CAR)-T cell therapy. A prior study demonstrated that cardiac injury and cardiovascular events in the form of elevated troponin and left ventricular systolic dysfunction are common post-CAR-T; in a cohort of 137 patients with post-CAR-T cytokine release syndrome (CRS), 21% had elevated troponin and 12% developed cardiovascular events including cardiac arrest, decompensated heart failure, and arrhythmias [65]. Notably in this study, a shorter time from CRS onset to the administration of the IL-6 inhibitor tocilizumab was associated with a lower rate of cardiovascular events [65].…”

Section: Immune Responses To Sars-cov-2 Infection and The Heartmentioning

confidence: 99%

“…A prior study demonstrated that cardiac injury and cardiovascular events in the form of elevated troponin and left ventricular systolic dysfunction are common post-CAR-T; in a cohort of 137 patients with post-CAR-T cytokine release syndrome (CRS), 21% had elevated troponin and 12% developed cardiovascular events including cardiac arrest, decompensated heart failure, and arrhythmias [65]. Notably in this study, a shorter time from CRS onset to the administration of the IL-6 inhibitor tocilizumab was associated with a lower rate of cardiovascular events [65]. Of note, tociluzumab may have some benefit in COVID-19 infection, suggesting a common mechanism of injury in the two settings [66].…”

Section: Immune Responses To Sars-cov-2 Infection and The Heartmentioning

confidence: 99%

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Cardiovascular Complications in Patients with COVID-19: Consequences of Viral Toxicities and Host Immune Response

et al. 2020

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Purpose of Review Coronavirus disease of 2019 (COVID-19) is a cause of significant morbidity and mortality worldwide. While cardiac injury has been demonstrated in critically ill COVID-19 patients, the mechanism of injury remains unclear. Here, we review our current knowledge of the biology of SARS-CoV-2 and the potential mechanisms of myocardial injury due to viral toxicities and host immune responses. Recent Findings A number of studies have reported an epidemiological association between history of cardiac disease and worsened outcome during COVID infection. Development of new onset myocardial injury during COVID-19 also increases mortality. While limited data exist, potential mechanisms of cardiac injury include direct viral entry through the angiotensinconverting enzyme 2 (ACE2) receptor and toxicity in host cells, hypoxia-related myocyte injury, and immune-mediated cytokine release syndrome. Potential treatments for reducing viral infection and excessive immune responses are also discussed. Summary COVID patients with cardiac disease history or acquire new cardiac injury are at an increased risk for in-hospital morbidity and mortality. More studies are needed to address the mechanism of cardiotoxicity and the treatments that can minimize permanent damage to the cardiovascular system.

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Section: Immune Responses To Sars-cov-2 Infection and The Heartmentioning

confidence: 99%

Section: Immune Responses To Sars-cov-2 Infection and The Heartmentioning

confidence: 99%

Cardiovascular Complications in Patients with COVID-19: Consequences of Viral Toxicities and Host Immune Response

et al. 2020

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“…An interesting observation made in this study was that patients with pre-existing cardiac structural abnormalities (increased left atrial size, increased LV mass or dimension) had baseline elevated troponins which translated into worse outcomes post treatment. Another reported finding of this study was that severity of CRS and delay in treating CRS with tocilizumab (1.7-fold increased risk with each 12-hour delay) led to worse CV outcomes [10]. Hence, this study postulates that elevated baseline troponin in the absence of existing acute coronary syndrome as well as severity of CRS can be considered as a surrogate for patients who are at increased risk for cardiotoxicity of CAR T-cell therapy.…”

Section: Reviewmentioning

confidence: 69%

“…In the study by Burstein et al, majority of the young patients (99%) had acute lymphocytic leukemia (ALL) [9]. Patients studied by Alvi et al were mostly treated for lymphomas (88%), while the study by Lefebvre et al also included majority of patients (90%) with lymphomas [10,11]. CAR T-cell therapy while still being investigated for acute myelogenous leukemia treatment has not yet been approved for it.…”

Section: Reviewmentioning

confidence: 99%

Cardiovascular Risk Profile of Chimeric Antigen Receptor T-cell Therapy

Ahmed

2020

Cureus

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Chimeric antigen receptor (CAR) T-cell therapy is a novel form of immunotherapy that has been recently introduced in clinical practice for the treatment of leukemias and lymphomas after being approved by United States Food and Drug Administration (USFDA). The risk profile of this treatment modality is not yet fully explored. As the survival of cancer patients is expected to rise due to new therapies being brought into practice, physicians are going to encounter side effects of these therapies. This may include both short-term and long-term effects. Having a good knowledge of these side effects can help the physicians recognize in advance the at-risk population and risk stratify them accordingly. Cardiac oncology is a growing field that involves the study of interaction between novel immunotherapies and their cardiac side effects. Knowing the cardiotoxicity profile of CAR T-cell therapy will help us choose the most appropriate patient population (those who can benefit the most without being at risk of harmful effects including cardiotoxicity) for the therapy. It will also help us recognize various cardiac complications, as they arise later during the lifetime of these cancer survivors.

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“…In ICI cardiotoxicity, blockade of intrinsic checkpoints by antibody administration leads to immune cell-mediated myocarditis, which is associated with significant morbidity and mortality. [4] Cardiotoxicity associated with CAR-T cells is related to CRS, a phenomenon marked by an exuberant release of inflammatory cytokines, with IL-6 thought to be an important mediator of this response [5]. Primary treatment for these immune therapy-related cardiotoxicities is different.…”

mentioning

confidence: 99%

COVID-19, Immuno-oncology and Cardiovascular Disease: Viewpoint from the Intersection

Siddiqi

Neilan

2020

J. of Cardiovasc. Trans. Res.

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Cardiovascular Events Among Adults Treated With Chimeric Antigen Receptor T-Cells (CAR-T)

Cited by 233 publications

References 34 publications

Cardiovascular Complications in Patients with COVID-19: Consequences of Viral Toxicities and Host Immune Response

Cardiovascular Complications in Patients with COVID-19: Consequences of Viral Toxicities and Host Immune Response

Cardiovascular Risk Profile of Chimeric Antigen Receptor T-cell Therapy

COVID-19, Immuno-oncology and Cardiovascular Disease: Viewpoint from the Intersection

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