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Prognostic impact of corticosteroids on efficacy of chimeric antigen receptor T-cell therapy in large B-cell lymphoma
Corticosteroids are commonly used for the management of severe toxicities associated with chimeric antigen receptor (CAR) T-cell therapy. However, it remains unclear whether their dose, duration, and timing may affect clinical efficacy. Here, we determined the impact of corticosteroids on clinical o...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Hematology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351896/ https://www.ncbi.nlm.nih.gov/pubmed/33534891 http://dx.doi.org/10.1182/blood.2020008865 |
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author | Strati, Paolo Ahmed, Sairah Furqan, Fateeha Fayad, Luis E. Lee, Hun J. Iyer, Swaminathan P. Nair, Ranjit Nastoupil, Loretta J. Parmar, Simrit Rodriguez, Maria A. Samaniego, Felipe Steiner, Raphael E. Wang, Michael Pinnix, Chelsea C. Horowitz, Sandra B. Feng, Lei Sun, Ryan Claussen, Catherine M. Hawkins, Misha C. Johnson, Nicole A. Singh, Prachee Mistry, Haleigh Johncy, Swapna Adkins, Sherry Kebriaei, Partow Shpall, Elizabeth J. Green, Michael R. Flowers, Christopher R. Westin, Jason Neelapu, Sattva S. |
author_facet | Strati, Paolo Ahmed, Sairah Furqan, Fateeha Fayad, Luis E. Lee, Hun J. Iyer, Swaminathan P. Nair, Ranjit Nastoupil, Loretta J. Parmar, Simrit Rodriguez, Maria A. Samaniego, Felipe Steiner, Raphael E. Wang, Michael Pinnix, Chelsea C. Horowitz, Sandra B. Feng, Lei Sun, Ryan Claussen, Catherine M. Hawkins, Misha C. Johnson, Nicole A. Singh, Prachee Mistry, Haleigh Johncy, Swapna Adkins, Sherry Kebriaei, Partow Shpall, Elizabeth J. Green, Michael R. Flowers, Christopher R. Westin, Jason Neelapu, Sattva S. |
author_sort | Strati, Paolo |
collection | PubMed |
description | Corticosteroids are commonly used for the management of severe toxicities associated with chimeric antigen receptor (CAR) T-cell therapy. However, it remains unclear whether their dose, duration, and timing may affect clinical efficacy. Here, we determined the impact of corticosteroids on clinical outcomes in patients with relapsed or refractory large B-cell lymphoma treated with standard of care anti-CD19 CAR T-cell therapy. Among 100 patients evaluated, 60 (60%) received corticosteroids for management of CAR T-cell therapy–associated toxicities. The median cumulative dexamethasone-equivalent dose was 186 mg (range, 8-1803) and the median duration of corticosteroid treatment was 9 days (range, 1-30). Corticosteroid treatment was started between days 0 and 7 in 45 (75%) patients and beyond day 7 in 15 (25%). After a median follow-up of 10 months (95% confidence interval, 8-12 months), use of higher cumulative dose of corticosteroids was associated with significantly shorter progression-free survival. More importantly, higher cumulative dose of corticosteroids, and prolonged and early use after CAR T-cell infusion were associated with significantly shorter overall survival. These results suggest that corticosteroids should be used at the lowest dose and for the shortest duration and their initiation should be delayed whenever clinically feasible while managing CAR T-cell therapy–associated toxicities. |
format | Online Article Text |
id | pubmed-8351896 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society of Hematology |
record_format | MEDLINE/PubMed |
spelling | pubmed-83518962021-08-18 Prognostic impact of corticosteroids on efficacy of chimeric antigen receptor T-cell therapy in large B-cell lymphoma Strati, Paolo Ahmed, Sairah Furqan, Fateeha Fayad, Luis E. Lee, Hun J. Iyer, Swaminathan P. Nair, Ranjit Nastoupil, Loretta J. Parmar, Simrit Rodriguez, Maria A. Samaniego, Felipe Steiner, Raphael E. Wang, Michael Pinnix, Chelsea C. Horowitz, Sandra B. Feng, Lei Sun, Ryan Claussen, Catherine M. Hawkins, Misha C. Johnson, Nicole A. Singh, Prachee Mistry, Haleigh Johncy, Swapna Adkins, Sherry Kebriaei, Partow Shpall, Elizabeth J. Green, Michael R. Flowers, Christopher R. Westin, Jason Neelapu, Sattva S. Blood Gene Therapy Corticosteroids are commonly used for the management of severe toxicities associated with chimeric antigen receptor (CAR) T-cell therapy. However, it remains unclear whether their dose, duration, and timing may affect clinical efficacy. Here, we determined the impact of corticosteroids on clinical outcomes in patients with relapsed or refractory large B-cell lymphoma treated with standard of care anti-CD19 CAR T-cell therapy. Among 100 patients evaluated, 60 (60%) received corticosteroids for management of CAR T-cell therapy–associated toxicities. The median cumulative dexamethasone-equivalent dose was 186 mg (range, 8-1803) and the median duration of corticosteroid treatment was 9 days (range, 1-30). Corticosteroid treatment was started between days 0 and 7 in 45 (75%) patients and beyond day 7 in 15 (25%). After a median follow-up of 10 months (95% confidence interval, 8-12 months), use of higher cumulative dose of corticosteroids was associated with significantly shorter progression-free survival. More importantly, higher cumulative dose of corticosteroids, and prolonged and early use after CAR T-cell infusion were associated with significantly shorter overall survival. These results suggest that corticosteroids should be used at the lowest dose and for the shortest duration and their initiation should be delayed whenever clinically feasible while managing CAR T-cell therapy–associated toxicities. American Society of Hematology 2021-06-10 /pmc/articles/PMC8351896/ /pubmed/33534891 http://dx.doi.org/10.1182/blood.2020008865 Text en © 2021 by The American Society of Hematology This article is made available via the PMC Open Access Subset for unrestricted reuse and analyses in any form or by any means with acknowledgment of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections. |
spellingShingle | Gene Therapy Strati, Paolo Ahmed, Sairah Furqan, Fateeha Fayad, Luis E. Lee, Hun J. Iyer, Swaminathan P. Nair, Ranjit Nastoupil, Loretta J. Parmar, Simrit Rodriguez, Maria A. Samaniego, Felipe Steiner, Raphael E. Wang, Michael Pinnix, Chelsea C. Horowitz, Sandra B. Feng, Lei Sun, Ryan Claussen, Catherine M. Hawkins, Misha C. Johnson, Nicole A. Singh, Prachee Mistry, Haleigh Johncy, Swapna Adkins, Sherry Kebriaei, Partow Shpall, Elizabeth J. Green, Michael R. Flowers, Christopher R. Westin, Jason Neelapu, Sattva S. Prognostic impact of corticosteroids on efficacy of chimeric antigen receptor T-cell therapy in large B-cell lymphoma |
title | Prognostic impact of corticosteroids on efficacy of chimeric antigen receptor T-cell therapy in large B-cell lymphoma |
title_full | Prognostic impact of corticosteroids on efficacy of chimeric antigen receptor T-cell therapy in large B-cell lymphoma |
title_fullStr | Prognostic impact of corticosteroids on efficacy of chimeric antigen receptor T-cell therapy in large B-cell lymphoma |
title_full_unstemmed | Prognostic impact of corticosteroids on efficacy of chimeric antigen receptor T-cell therapy in large B-cell lymphoma |
title_short | Prognostic impact of corticosteroids on efficacy of chimeric antigen receptor T-cell therapy in large B-cell lymphoma |
title_sort | prognostic impact of corticosteroids on efficacy of chimeric antigen receptor t-cell therapy in large b-cell lymphoma |
topic | Gene Therapy |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351896/ https://www.ncbi.nlm.nih.gov/pubmed/33534891 http://dx.doi.org/10.1182/blood.2020008865 |
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