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Cardiovascular events in patients treated with chimeric antigen receptor T-cell therapy for aggressive B-cell lymphoma

Standard of care (SOC) chimeric antigen receptor (CAR) T-cell therapies such as axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are associated with multisystem toxicities. There is limited information available about cardiovascular (CV) events associated with SOC axi-cel or tisa-ce...

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Autores principales: Steiner, Raphael E., Banchs, Jose, Koutroumpakis, Efstratios, Becnel, Melody, Gutierrez, Cristina, Strati, Paolo, Pinnix, Chelsea C., Feng, Lei, Rondon, Gabriela, Claussen, Catherine, Palaskas, Nicolas, Karimzad, Kaveh, Ahmed, Sairah, Neelapu, Sattva S., Shpall, Elizabeth, Wang, Michael, Vega, Francisco, Westin, Jason, Nastoupil, Loretta J., Deswal, Anita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Fondazione Ferrata Storti 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9244830/
https://www.ncbi.nlm.nih.gov/pubmed/34758610
http://dx.doi.org/10.3324/haematol.2021.280009
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author Steiner, Raphael E.
Banchs, Jose
Koutroumpakis, Efstratios
Becnel, Melody
Gutierrez, Cristina
Strati, Paolo
Pinnix, Chelsea C.
Feng, Lei
Rondon, Gabriela
Claussen, Catherine
Palaskas, Nicolas
Karimzad, Kaveh
Ahmed, Sairah
Neelapu, Sattva S.
Shpall, Elizabeth
Wang, Michael
Vega, Francisco
Westin, Jason
Nastoupil, Loretta J.
Deswal, Anita
author_facet Steiner, Raphael E.
Banchs, Jose
Koutroumpakis, Efstratios
Becnel, Melody
Gutierrez, Cristina
Strati, Paolo
Pinnix, Chelsea C.
Feng, Lei
Rondon, Gabriela
Claussen, Catherine
Palaskas, Nicolas
Karimzad, Kaveh
Ahmed, Sairah
Neelapu, Sattva S.
Shpall, Elizabeth
Wang, Michael
Vega, Francisco
Westin, Jason
Nastoupil, Loretta J.
Deswal, Anita
author_sort Steiner, Raphael E.
collection PubMed
description Standard of care (SOC) chimeric antigen receptor (CAR) T-cell therapies such as axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are associated with multisystem toxicities. There is limited information available about cardiovascular (CV) events associated with SOC axi-cel or tisa-cel. Patients with CV comorbidities, organ dysfunction, or lower performance status were often excluded in the clinical trials leading to their Food and Drug Adminsitration approval. An improved understanding of CV toxicities in the real-world setting will better inform therapy selection and management of patients receiving these cellular therapies. Here, we retrospectively reviewed the characteristics and outcomes of adult patients with relapsed/refractory large B-cell lymphoma treated with SOC axi-cel or tisa-cel. Among the 165 patients evaluated, 27 (16%) developed at least one 30-day (30-d) major adverse CV event (MACE). Cumulatively, these patients experienced 21 arrhythmias, four exacerbations of heart failure/cardiomyopathy, four cerebrovascular accidents, three myocardial infarctions, and one patient died due to myocardial infaction. Factors significantly associated with an increased risk of 30-d MACE included age ≥60 years, an earlier start of cytokine release syndrome (CRS), CRS ≥ grade 3, long duration of CRS, and use of tocilizumab. After a median follow-up time of 16.2 months (range, 14.3-19.1), the occurrence of 30-d MACE was not significantly associated with progression-free survival or with overall survival. Our results suggest that the occurrence of 30-d MACE is more frequent among patients who are elderly, with early, severe, and prolonged CRS. However, with limited follow-up, larger prospective studies are needed, and multidisciplinary management of these patients is recommended.
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spelling pubmed-92448302022-07-07 Cardiovascular events in patients treated with chimeric antigen receptor T-cell therapy for aggressive B-cell lymphoma Steiner, Raphael E. Banchs, Jose Koutroumpakis, Efstratios Becnel, Melody Gutierrez, Cristina Strati, Paolo Pinnix, Chelsea C. Feng, Lei Rondon, Gabriela Claussen, Catherine Palaskas, Nicolas Karimzad, Kaveh Ahmed, Sairah Neelapu, Sattva S. Shpall, Elizabeth Wang, Michael Vega, Francisco Westin, Jason Nastoupil, Loretta J. Deswal, Anita Haematologica Article - Cell Therapy and Immunotherapy Standard of care (SOC) chimeric antigen receptor (CAR) T-cell therapies such as axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are associated with multisystem toxicities. There is limited information available about cardiovascular (CV) events associated with SOC axi-cel or tisa-cel. Patients with CV comorbidities, organ dysfunction, or lower performance status were often excluded in the clinical trials leading to their Food and Drug Adminsitration approval. An improved understanding of CV toxicities in the real-world setting will better inform therapy selection and management of patients receiving these cellular therapies. Here, we retrospectively reviewed the characteristics and outcomes of adult patients with relapsed/refractory large B-cell lymphoma treated with SOC axi-cel or tisa-cel. Among the 165 patients evaluated, 27 (16%) developed at least one 30-day (30-d) major adverse CV event (MACE). Cumulatively, these patients experienced 21 arrhythmias, four exacerbations of heart failure/cardiomyopathy, four cerebrovascular accidents, three myocardial infarctions, and one patient died due to myocardial infaction. Factors significantly associated with an increased risk of 30-d MACE included age ≥60 years, an earlier start of cytokine release syndrome (CRS), CRS ≥ grade 3, long duration of CRS, and use of tocilizumab. After a median follow-up time of 16.2 months (range, 14.3-19.1), the occurrence of 30-d MACE was not significantly associated with progression-free survival or with overall survival. Our results suggest that the occurrence of 30-d MACE is more frequent among patients who are elderly, with early, severe, and prolonged CRS. However, with limited follow-up, larger prospective studies are needed, and multidisciplinary management of these patients is recommended. Fondazione Ferrata Storti 2021-11-11 /pmc/articles/PMC9244830/ /pubmed/34758610 http://dx.doi.org/10.3324/haematol.2021.280009 Text en Copyright© 2022 Ferrata Storti Foundation https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Article - Cell Therapy and Immunotherapy
Steiner, Raphael E.
Banchs, Jose
Koutroumpakis, Efstratios
Becnel, Melody
Gutierrez, Cristina
Strati, Paolo
Pinnix, Chelsea C.
Feng, Lei
Rondon, Gabriela
Claussen, Catherine
Palaskas, Nicolas
Karimzad, Kaveh
Ahmed, Sairah
Neelapu, Sattva S.
Shpall, Elizabeth
Wang, Michael
Vega, Francisco
Westin, Jason
Nastoupil, Loretta J.
Deswal, Anita
Cardiovascular events in patients treated with chimeric antigen receptor T-cell therapy for aggressive B-cell lymphoma
title Cardiovascular events in patients treated with chimeric antigen receptor T-cell therapy for aggressive B-cell lymphoma
title_full Cardiovascular events in patients treated with chimeric antigen receptor T-cell therapy for aggressive B-cell lymphoma
title_fullStr Cardiovascular events in patients treated with chimeric antigen receptor T-cell therapy for aggressive B-cell lymphoma
title_full_unstemmed Cardiovascular events in patients treated with chimeric antigen receptor T-cell therapy for aggressive B-cell lymphoma
title_short Cardiovascular events in patients treated with chimeric antigen receptor T-cell therapy for aggressive B-cell lymphoma
title_sort cardiovascular events in patients treated with chimeric antigen receptor t-cell therapy for aggressive b-cell lymphoma
topic Article - Cell Therapy and Immunotherapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9244830/
https://www.ncbi.nlm.nih.gov/pubmed/34758610
http://dx.doi.org/10.3324/haematol.2021.280009
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