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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Hematology 2021
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.
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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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