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Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial
High-risk large B-cell lymphoma (LBCL) has poor outcomes with standard first-line chemoimmunotherapy. In the phase 2, multicenter, single-arm ZUMA-12 study (ClinicalTrials.gov NCT03761056) we evaluated axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018426/ https://www.ncbi.nlm.nih.gov/pubmed/35314842 http://dx.doi.org/10.1038/s41591-022-01731-4 |
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author | Neelapu, Sattva S. Dickinson, Michael Munoz, Javier Ulrickson, Matthew L. Thieblemont, Catherine Oluwole, Olalekan O. Herrera, Alex F. Ujjani, Chaitra S. Lin, Yi Riedell, Peter A. Kekre, Natasha de Vos, Sven Lui, Christine Milletti, Francesca Dong, Jinghui Xu, Hairong Chavez, Julio C. |
author_facet | Neelapu, Sattva S. Dickinson, Michael Munoz, Javier Ulrickson, Matthew L. Thieblemont, Catherine Oluwole, Olalekan O. Herrera, Alex F. Ujjani, Chaitra S. Lin, Yi Riedell, Peter A. Kekre, Natasha de Vos, Sven Lui, Christine Milletti, Francesca Dong, Jinghui Xu, Hairong Chavez, Julio C. |
author_sort | Neelapu, Sattva S. |
collection | PubMed |
description | High-risk large B-cell lymphoma (LBCL) has poor outcomes with standard first-line chemoimmunotherapy. In the phase 2, multicenter, single-arm ZUMA-12 study (ClinicalTrials.gov NCT03761056) we evaluated axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, as part of first-line treatment in 40 patients with high-risk LBCL. This trial has completed accrual. The primary outcome was complete response rate (CRR). Secondary outcomes were objective response rate (ORR), duration of response (DOR), event-free survival (EFS), progression-free survival (PFS), overall survival (OS), assessment of safety, central nervous system (CNS) relapse and blood levels of CAR T cells and cytokines. The primary endpoint in efficacy-evaluable patients (n = 37) was met, with 78% CRR (95% confidence interval (CI), 62–90) and 89% ORR (95% CI, 75–97). As of 17 May 2021 (median follow-up, 15.9 months), 73% of patients remained in objective response; median DOR, EFS and PFS were not reached. Grade ≥3 cytokine release syndrome (CRS) and neurologic events occurred in three patients (8%) and nine patients (23%), respectively. There were no treatment-related grade 5 events. Robust CAR T-cell expansion occurred in all patients with a median time to peak of 8 days. We conclude that axi-cel is highly effective as part of first-line therapy for high-risk LBCL, with a manageable safety profile. |
format | Online Article Text |
id | pubmed-9018426 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-90184262022-04-29 Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial Neelapu, Sattva S. Dickinson, Michael Munoz, Javier Ulrickson, Matthew L. Thieblemont, Catherine Oluwole, Olalekan O. Herrera, Alex F. Ujjani, Chaitra S. Lin, Yi Riedell, Peter A. Kekre, Natasha de Vos, Sven Lui, Christine Milletti, Francesca Dong, Jinghui Xu, Hairong Chavez, Julio C. Nat Med Article High-risk large B-cell lymphoma (LBCL) has poor outcomes with standard first-line chemoimmunotherapy. In the phase 2, multicenter, single-arm ZUMA-12 study (ClinicalTrials.gov NCT03761056) we evaluated axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, as part of first-line treatment in 40 patients with high-risk LBCL. This trial has completed accrual. The primary outcome was complete response rate (CRR). Secondary outcomes were objective response rate (ORR), duration of response (DOR), event-free survival (EFS), progression-free survival (PFS), overall survival (OS), assessment of safety, central nervous system (CNS) relapse and blood levels of CAR T cells and cytokines. The primary endpoint in efficacy-evaluable patients (n = 37) was met, with 78% CRR (95% confidence interval (CI), 62–90) and 89% ORR (95% CI, 75–97). As of 17 May 2021 (median follow-up, 15.9 months), 73% of patients remained in objective response; median DOR, EFS and PFS were not reached. Grade ≥3 cytokine release syndrome (CRS) and neurologic events occurred in three patients (8%) and nine patients (23%), respectively. There were no treatment-related grade 5 events. Robust CAR T-cell expansion occurred in all patients with a median time to peak of 8 days. We conclude that axi-cel is highly effective as part of first-line therapy for high-risk LBCL, with a manageable safety profile. Nature Publishing Group US 2022-03-21 2022 /pmc/articles/PMC9018426/ /pubmed/35314842 http://dx.doi.org/10.1038/s41591-022-01731-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Neelapu, Sattva S. Dickinson, Michael Munoz, Javier Ulrickson, Matthew L. Thieblemont, Catherine Oluwole, Olalekan O. Herrera, Alex F. Ujjani, Chaitra S. Lin, Yi Riedell, Peter A. Kekre, Natasha de Vos, Sven Lui, Christine Milletti, Francesca Dong, Jinghui Xu, Hairong Chavez, Julio C. Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial |
title | Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial |
title_full | Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial |
title_fullStr | Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial |
title_full_unstemmed | Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial |
title_short | Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial |
title_sort | axicabtagene ciloleucel as first-line therapy in high-risk large b-cell lymphoma: the phase 2 zuma-12 trial |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018426/ https://www.ncbi.nlm.nih.gov/pubmed/35314842 http://dx.doi.org/10.1038/s41591-022-01731-4 |
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