Evaluation of all-cause mortality and cardiovascular safety in patients receiving chimeric antigen receptor T cell therapy: a prospective cohort studyResearch in context
Summary: Background: Assessment of cardiovascular risk is critical for patients with cancer. Previous retrospective studies suggest potential cardiotoxicity of CAR T cell therapies. We aimed to prospectively assess cardiotoxicity and the predictive value of cardiac biomarkers and classical risk fac...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | EClinicalMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S258953702400083X |
| _version_ | 1797292865077903360 |
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| author | Felix Korell Lukas Entenmann Sebastian Romann Evangelos Giannitsis Anita Schmitt Carsten Müller-Tidow Norbert Frey Peter Dreger Michael Schmitt Lorenz H Lehmann |
| author_facet | Felix Korell Lukas Entenmann Sebastian Romann Evangelos Giannitsis Anita Schmitt Carsten Müller-Tidow Norbert Frey Peter Dreger Michael Schmitt Lorenz H Lehmann |
| author_sort | Felix Korell |
| collection | DOAJ |
| description | Summary: Background: Assessment of cardiovascular risk is critical for patients with cancer. Previous retrospective studies suggest potential cardiotoxicity of CAR T cell therapies. We aimed to prospectively assess cardiotoxicity and the predictive value of cardiac biomarkers and classical risk factors (age, cardiac function, diabetes, arterial hypertension, smoking) for cardiac events and all-cause mortality (ACM). Methods: In this prospective cohort study, all patients treated with CAR T cell constructs (axi-cel, tisa-cel, brexu-cel, ide-cel, or the 3rd generation CAR HD-CAR-1) from Oct 1, 2018, to Sept 30, 2022 at the University Hospital Heidelberg were included. Surveillance included cardiac assessment with biomarkers (high-sensitive Troponin T (hs-cTnT), N-terminal brain natriuretic peptide (NT-proBNP)), 12-lead-ECG, and 2D echocardiography. ACM was defined as the primary study endpoint, while cardiotoxicity, defined by clinical syndromes of heart failure or decline in ejection fraction, served as a secondary endpoint. Findings: Overall, 137 patients (median age 60, range 20–83, IQR 16), were included in the study. 46 patients died during the follow up period (median 0.75 years, range 0.02–4.33, IQR 0.89) 57 month, with a median survival of 0.57 years (range 0.03–2.38 years, IQR 0.79). A septal wall thickness above 11 mm (HR 2.48, 95%-CI = 1.10–5.67, p = 0.029) was associated with an increased risk of ACM, with a trend seen for reduced left ventricular ejection fraction prior to therapy (LVEF <40%; HR 9.17, 95%-CI = 1.30–183.11, p = 0.051). Secondary endpoint was reached by 93 patients while no baseline parameter was able to predict an elevated risk. However, hs-cTnT change from baseline of 50% or more during the first 14 days after CAR infusion predicted ACM (HR 3.81, 95%-CI = 1.58–9.45; p = 0.003). None of the baseline characteristics was able to predict the incidence of cardiac events. Interpretation: Reduced pre-lymphodepletion ejection fraction and early post-infusion biomarker kinetics may be associated with increased ACM and cardiotoxicity events. These findings may help to identify patients who could benefit from intensified cardio-oncological surveillance. Funding: The German Center for Cardiovascular Research, German Research Foundation, and the Federal Ministry of Education and Research. |
| first_indexed | 2024-03-07T20:03:44Z |
| format | Article |
| id | doaj.art-073119b3fda1485ab34c0e1b991554bd |
| institution | Directory Open Access Journal |
| issn | 2589-5370 |
| language | English |
| last_indexed | 2024-03-07T20:03:44Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EClinicalMedicine |
| spelling | doaj.art-073119b3fda1485ab34c0e1b991554bd2024-02-28T05:13:59ZengElsevierEClinicalMedicine2589-53702024-03-0169102504Evaluation of all-cause mortality and cardiovascular safety in patients receiving chimeric antigen receptor T cell therapy: a prospective cohort studyResearch in contextFelix Korell0Lukas Entenmann1Sebastian Romann2Evangelos Giannitsis3Anita Schmitt4Carsten Müller-Tidow5Norbert Frey6Peter Dreger7Michael Schmitt8Lorenz H Lehmann9Department of Hematology, Oncology & Rheumatology, University Hospital Heidelberg, Heidelberg, GermanyDepartment of Cardiology, Angiology & Pulmonology, University Hospital Heidelberg, Heidelberg, GermanyDepartment of Cardiology, Angiology & Pulmonology, University Hospital Heidelberg, Heidelberg, GermanyDepartment of Cardiology, Angiology & Pulmonology, University Hospital Heidelberg, Heidelberg, GermanyDepartment of Hematology, Oncology & Rheumatology, University Hospital Heidelberg, Heidelberg, GermanyDepartment of Hematology, Oncology & Rheumatology, University Hospital Heidelberg, Heidelberg, GermanyDepartment of Cardiology, Angiology & Pulmonology, University Hospital Heidelberg, Heidelberg, GermanyDepartment of Hematology, Oncology & Rheumatology, University Hospital Heidelberg, Heidelberg, GermanyDepartment of Hematology, Oncology & Rheumatology, University Hospital Heidelberg, Heidelberg, GermanyDepartment of Cardiology, Angiology & Pulmonology, University Hospital Heidelberg, Heidelberg, Germany; Corresponding author. Department of Internal Medicine III: Cardiology, Angiology & Pulmonology, Cardio-Oncology Unit, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.Summary: Background: Assessment of cardiovascular risk is critical for patients with cancer. Previous retrospective studies suggest potential cardiotoxicity of CAR T cell therapies. We aimed to prospectively assess cardiotoxicity and the predictive value of cardiac biomarkers and classical risk factors (age, cardiac function, diabetes, arterial hypertension, smoking) for cardiac events and all-cause mortality (ACM). Methods: In this prospective cohort study, all patients treated with CAR T cell constructs (axi-cel, tisa-cel, brexu-cel, ide-cel, or the 3rd generation CAR HD-CAR-1) from Oct 1, 2018, to Sept 30, 2022 at the University Hospital Heidelberg were included. Surveillance included cardiac assessment with biomarkers (high-sensitive Troponin T (hs-cTnT), N-terminal brain natriuretic peptide (NT-proBNP)), 12-lead-ECG, and 2D echocardiography. ACM was defined as the primary study endpoint, while cardiotoxicity, defined by clinical syndromes of heart failure or decline in ejection fraction, served as a secondary endpoint. Findings: Overall, 137 patients (median age 60, range 20–83, IQR 16), were included in the study. 46 patients died during the follow up period (median 0.75 years, range 0.02–4.33, IQR 0.89) 57 month, with a median survival of 0.57 years (range 0.03–2.38 years, IQR 0.79). A septal wall thickness above 11 mm (HR 2.48, 95%-CI = 1.10–5.67, p = 0.029) was associated with an increased risk of ACM, with a trend seen for reduced left ventricular ejection fraction prior to therapy (LVEF <40%; HR 9.17, 95%-CI = 1.30–183.11, p = 0.051). Secondary endpoint was reached by 93 patients while no baseline parameter was able to predict an elevated risk. However, hs-cTnT change from baseline of 50% or more during the first 14 days after CAR infusion predicted ACM (HR 3.81, 95%-CI = 1.58–9.45; p = 0.003). None of the baseline characteristics was able to predict the incidence of cardiac events. Interpretation: Reduced pre-lymphodepletion ejection fraction and early post-infusion biomarker kinetics may be associated with increased ACM and cardiotoxicity events. These findings may help to identify patients who could benefit from intensified cardio-oncological surveillance. Funding: The German Center for Cardiovascular Research, German Research Foundation, and the Federal Ministry of Education and Research.http://www.sciencedirect.com/science/article/pii/S258953702400083XCardiotoxicityCAR T cellsCardiac biomarkersRisk stratification |
| spellingShingle | Felix Korell Lukas Entenmann Sebastian Romann Evangelos Giannitsis Anita Schmitt Carsten Müller-Tidow Norbert Frey Peter Dreger Michael Schmitt Lorenz H Lehmann Evaluation of all-cause mortality and cardiovascular safety in patients receiving chimeric antigen receptor T cell therapy: a prospective cohort studyResearch in context EClinicalMedicine Cardiotoxicity CAR T cells Cardiac biomarkers Risk stratification |
| title | Evaluation of all-cause mortality and cardiovascular safety in patients receiving chimeric antigen receptor T cell therapy: a prospective cohort studyResearch in context |
| title_full | Evaluation of all-cause mortality and cardiovascular safety in patients receiving chimeric antigen receptor T cell therapy: a prospective cohort studyResearch in context |
| title_fullStr | Evaluation of all-cause mortality and cardiovascular safety in patients receiving chimeric antigen receptor T cell therapy: a prospective cohort studyResearch in context |
| title_full_unstemmed | Evaluation of all-cause mortality and cardiovascular safety in patients receiving chimeric antigen receptor T cell therapy: a prospective cohort studyResearch in context |
| title_short | Evaluation of all-cause mortality and cardiovascular safety in patients receiving chimeric antigen receptor T cell therapy: a prospective cohort studyResearch in context |
| title_sort | evaluation of all cause mortality and cardiovascular safety in patients receiving chimeric antigen receptor t cell therapy a prospective cohort studyresearch in context |
| topic | Cardiotoxicity CAR T cells Cardiac biomarkers Risk stratification |
| url | http://www.sciencedirect.com/science/article/pii/S258953702400083X |
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