Adverse Cardiovascular and Pulmonary Events Associated With Chimeric Antigen Receptor T-Cell Therapy

Goldman, Adam; Maor, Elad; Bomze, David; Liu, Jennifer E.; Herrmann, Joerg; Fein, Joshua; Steingart, Richard M.; Mahmood, Syed; Schaffer, Wendy; Perales, Miguel-Ángel; Shouval, Roni

doi:10.1016/j.jacc.2021.08.044

Cited by 77 publications

(80 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cytokine-induced fluid retention and/or systemic high vascular permeability is a possible cause of rapid accumulation of pericardial fluid ( 15 , 16 ). The clinical features of severe CRS resemble those of capillary leak syndrome ( 4 , 5 , 15 , 16 ). Pericardial effusion is reported to occur in 11% of patients with idiopathic capillary leak syndrome and can be life-threatening ( 17 , 18 ).…”

Section: Discussionmentioning

confidence: 96%

“…However, this novel therapy frequently causes CRS by over-activation of the immune system and subsequent elevation of cytokines such as interferon-gamma, tumor necrosis factor-alpha, and interleukin (IL)-6 ( 10 ). In recent years, there has been an increase in the number of reports on cardiovascular events after CAR-T cell therapy with or without overlapping CRS ( 4 , 5 ). To our knowledge, this is the first report of a case of cardiac tamponade associated with CRS after CAR-T cell therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Pericarditis or pericardial effusion after CAR-T cell therapy is rare, with a total incidence rate of 0.4%, and two-thirds of patients with pericardial disease have concurrent CRS ( 5 ). The underlying mechanism of pericardial disease after CAR-T cell therapy has not been well clarified.…”

Section: Discussionmentioning

confidence: 99%

“…Cardiovascular complications such as heart failure, arrhythmia, and pericardial disease due to CAR-T cell therapy have been reported and shown to be strongly related to CRS. However, the clinical features and management of CRS have not yet been well defined ( 4 , 5 ). Herein, we describe a case of acute pericardial effusion with cardiac tamponade associated with CRS after CAR-T cell therapy.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Case Report: Cardiac Tamponade in Association With Cytokine Release Syndrome Following CAR-T Cell Therapy

Moriyama

Fukata

Yamaguchi

et al. 2022

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Chimeric antigen receptor T (CAR-T) cell therapy has been shown to have substantial efficacy against refractory hematopoietic malignancies. However, it frequently causes cytokine release syndrome (CRS) as a treatment-specific adverse event. Although cardiovascular events associated with CAR-T cell therapy have been increasingly reported recently, pericardial disease is a rare complication and its clinical course is not well characterized. Here, we report a case of acute pericardial effusion with cardiac tamponade after CAR-T cell therapy.Case SummaryA 59-year-old man with refractory diffuse large B-cell lymphoma underwent CAR-T cell therapy. Grade 2 CRS was observed on day 0; it progressed to grade 4 on day 7 and was accompanied by a fever over 39°C, hypoxia requiring intubation, hypotension requiring the use of a vasopressor agent, and supraventricular tachycardia. Although cardiac function was preserved, marked pericardial effusion with the collapse of the right heart was detected on echocardiography. Since pericardiocentesis was considered to have a high complication risk due to severe myelosuppression, medications for CRS were prioritized. Tocilizumab, an interleukin-6 inhibitor, and high-dose methylprednisolone (1 g/day for 3 days) were administered for the management of severe CRS. On day 8, the pericardial effusion decreased, and the hemodynamic status markedly stabilized. CRS did not exacerbate after the steroid dose was reduced. Further, lymphoma size reduced after the induction of CAR-T cell therapy, and tumor regrowth was not noted at 3 months after CAR-T cell infusion.ConclusionInterleukin-6 pathway inhibitors and corticosteroid therapy should be considered in the context of CRS for significant pericardial effusion after CAR-T cell therapy in the acute phase.

show abstract

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Case Report: Cardiac Tamponade in Association With Cytokine Release Syndrome Following CAR-T Cell Therapy

Moriyama

Fukata

Yamaguchi

et al. 2022

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

show abstract

“… 2 , 12 , 13 , 27 , 34 Pharmacovigilance data recently showed relative mortality of 30.9% in patients with CV and pulmonary adverse events (CPAEs) compared with 17.4% in patients with CRS in the setting of CAR-T cell therapy, underscoring the imminent need for the management of these complications. 32 With the transition of CAR-T cell therapy to the standard of care and the increasing number of patients with pre-existing CV diseases, the characterization of CV side effects is of crucial importance. Particularly regarding the cardiocirculatory stress caused by CRS, sufficient cardiac reserve capacity appears to be essential to avoid life-threatening complications.…”

Section: Cardiovascular Adverse Eventsmentioning

confidence: 99%

Cardiotoxicity from chimeric antigen receptor-T cell therapy for advanced malignancies

Totzeck

Michel

Lin

et al. 2022

European Heart Journal

Self Cite

View full text Add to dashboard Cite

Chimeric antigen receptor (CAR)-T cell therapy is the next revolutionary advance in cancer therapy. By using ex vivo engineered T cells to specifically target antigens, a targeted immune reaction is induced. Chimeric antigen receptor-T cell therapy is approved for patients suffering from advanced and refractory B cell and plasma cell malignancies and is undergoing testing for various other haematologic and solid malignancies. In the process of triggering an anticancer immune reaction, a systemic inflammatory response can emerge as cytokine release syndrome (CRS). The severity of CRS is highly variable across patients, ranging from mild flu-like symptoms to fulminant hyperinflammatory states with excessive immune activation, associated multiorgan failure and high mortality risk. Cytokine release syndrome is also an important factor for adverse cardiovascular (CV) events. Sinus tachycardia and hypotension are the most common reflections, similar to what is seen with other systemic inflammatory response syndromes. Corrected QT interval prolongation and tachyarrhythmias, including ventricular arrhythmias and atrial fibrillation, also show a close link with CRS. Events of myocardial ischaemia and venous thromboembolism can be provoked during CAR-T cell therapy. Although not as closely related to CRS, changes in cardiac function can be observed to the point of heart failure and cardiogenic shock. This may also be encountered in patients with severe valvular heart disease in the setting of CRS. This review will discuss the pertinent CV risks of the growing field of CAR-T cell therapy for today’s cardiologists, including incidence, characteristics, and treatment options, and will conclude with an integrated management algorithm.

show abstract

CAR‐T cell therapeutic avenue for fighting cardiac fibrosis: Roadblocks and perspectives

Abdalla,

Miao,

Ahmed

et al. 2024

Cell Biochemistry & Function

View full text Add to dashboard Cite

Heart diseases remain the primary cause of human mortality in the world. Although conventional therapeutic opportunities fail to halt or recover cardiac fibrosis, the promising clinical results and therapeutic efficacy of engineered chimeric antigen receptor (CAR) T cell therapy show several advancements. However, the current models of CAR‐T cells need further improvement since the T cells are associated with the triggering of excessive inflammatory cytokines that directly affect cardiac functions. Thus, the current study highlights the critical function of heart immune cells in tissue fibrosis and repair. The study also confirms CAR‐T cell as an emerging therapeutic for treating cardiac fibrosis, explores the current roadblocks to CAR‐T cell therapy, and considers future outlooks for research development.

show abstract

Adverse Cardiovascular and Pulmonary Events Associated With Chimeric Antigen Receptor T-Cell Therapy

Cited by 77 publications

References 34 publications

Case Report: Cardiac Tamponade in Association With Cytokine Release Syndrome Following CAR-T Cell Therapy

Case Report: Cardiac Tamponade in Association With Cytokine Release Syndrome Following CAR-T Cell Therapy

Cardiotoxicity from chimeric antigen receptor-T cell therapy for advanced malignancies

CAR‐T cell therapeutic avenue for fighting cardiac fibrosis: Roadblocks and perspectives

Contact Info

Product

Resources

About