Cargando…

The Autologous Hematopoietic Stem Cells Transplantation Combination-Based Chimeric Antigen Receptor T-Cell Therapy Improves Outcomes of Relapsed/Refractory Central Nervous System B-Cell Lymphoma

OBJECTIVE: The objective is to explore the effectiveness and safety of CAR T-cell therapy in advanced relapsed/refractory central nervous system B-cell lymphoma and compare the impact of autologous stem cell transplantation (ASCT) plus CAR T-cell therapy versus sequential CART therapy on the surviva...

Descripción completa

Detalles Bibliográficos
Autores principales: Xue, Fei, Zheng, Peihao, Liu, Rui, Feng, Shaomei, Guo, Yuelu, Shi, Hui, Liu, Haidi, Deng, Biping, Xu, Teng, Ke, Xiaoyan, Hu, Kai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9726247/
https://www.ncbi.nlm.nih.gov/pubmed/36483984
http://dx.doi.org/10.1155/2022/2900310
_version_ 1784844732780773376
author Xue, Fei
Zheng, Peihao
Liu, Rui
Feng, Shaomei
Guo, Yuelu
Shi, Hui
Liu, Haidi
Deng, Biping
Xu, Teng
Ke, Xiaoyan
Hu, Kai
author_facet Xue, Fei
Zheng, Peihao
Liu, Rui
Feng, Shaomei
Guo, Yuelu
Shi, Hui
Liu, Haidi
Deng, Biping
Xu, Teng
Ke, Xiaoyan
Hu, Kai
author_sort Xue, Fei
collection PubMed
description OBJECTIVE: The objective is to explore the effectiveness and safety of CAR T-cell therapy in advanced relapsed/refractory central nervous system B-cell lymphoma and compare the impact of autologous stem cell transplantation (ASCT) plus CAR T-cell therapy versus sequential CART therapy on the survival of patients. METHODS: The retrospective analysis was based on the data of 17 patients with advanced relapsed/refractory central nervous system B-cell lymphoma. Bridging chemotherapy was applied before CAR T-cell infusion to further reduce the tumor burden. For patients with autologous hematopoietic stem cell successful collection, CD19/20/22CAR T-cell immunotherapy following ASCT was performed with the thiotepa-containing conditioning regimen, while sequential CD19/CD20/CD22CAR T-cell therapy was applied. For lymphodepletion, patients received bendamustine or fludarabine monotherapy or fludarabine combined with cyclophosphamide pre-CART-cell infusion. RESULTS: Out of the 17 patients, 8 completed ASCT plus CART cell therapy, while 9 patients completed CART cell alone therapy. In efficacy assessment at 3 months after infusion, the objective response rate (ORR) was 12/17 (71%) and the complete response rate (CRR) was 11/17 (65%). The CRR of the ASCT group and non-ASCT was 100% and 44.4%, respectively (P < 0.01). The median progression-free survival was 16.3 (2.6–24.5) months, and the median overall survival was 19.3 (6–24.5) months. Patients who underwent ASCT plus CART cell therapy had significantly longer PFS (P < 0.01) and OS (P < 0.01). Grade 3 or higher immune effector cell-associated neurologic toxicity syndrome (≥grade 3 ICANS) and cytokine release syndrome (≥grade 3 CRS) events occurred in 29% and 41% of the patients, respectively. No treatment-related death occurred. CONCLUSION: The CAR T-cell therapy could augment its efficacy in the treatment of advanced relapsed/refractory CNS B-cell lymphoma, while ASCT in combination with CART can induce durable responses and OS with a manageable side effect.
format Online
Article
Text
id pubmed-9726247
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-97262472022-12-07 The Autologous Hematopoietic Stem Cells Transplantation Combination-Based Chimeric Antigen Receptor T-Cell Therapy Improves Outcomes of Relapsed/Refractory Central Nervous System B-Cell Lymphoma Xue, Fei Zheng, Peihao Liu, Rui Feng, Shaomei Guo, Yuelu Shi, Hui Liu, Haidi Deng, Biping Xu, Teng Ke, Xiaoyan Hu, Kai J Oncol Research Article OBJECTIVE: The objective is to explore the effectiveness and safety of CAR T-cell therapy in advanced relapsed/refractory central nervous system B-cell lymphoma and compare the impact of autologous stem cell transplantation (ASCT) plus CAR T-cell therapy versus sequential CART therapy on the survival of patients. METHODS: The retrospective analysis was based on the data of 17 patients with advanced relapsed/refractory central nervous system B-cell lymphoma. Bridging chemotherapy was applied before CAR T-cell infusion to further reduce the tumor burden. For patients with autologous hematopoietic stem cell successful collection, CD19/20/22CAR T-cell immunotherapy following ASCT was performed with the thiotepa-containing conditioning regimen, while sequential CD19/CD20/CD22CAR T-cell therapy was applied. For lymphodepletion, patients received bendamustine or fludarabine monotherapy or fludarabine combined with cyclophosphamide pre-CART-cell infusion. RESULTS: Out of the 17 patients, 8 completed ASCT plus CART cell therapy, while 9 patients completed CART cell alone therapy. In efficacy assessment at 3 months after infusion, the objective response rate (ORR) was 12/17 (71%) and the complete response rate (CRR) was 11/17 (65%). The CRR of the ASCT group and non-ASCT was 100% and 44.4%, respectively (P < 0.01). The median progression-free survival was 16.3 (2.6–24.5) months, and the median overall survival was 19.3 (6–24.5) months. Patients who underwent ASCT plus CART cell therapy had significantly longer PFS (P < 0.01) and OS (P < 0.01). Grade 3 or higher immune effector cell-associated neurologic toxicity syndrome (≥grade 3 ICANS) and cytokine release syndrome (≥grade 3 CRS) events occurred in 29% and 41% of the patients, respectively. No treatment-related death occurred. CONCLUSION: The CAR T-cell therapy could augment its efficacy in the treatment of advanced relapsed/refractory CNS B-cell lymphoma, while ASCT in combination with CART can induce durable responses and OS with a manageable side effect. Hindawi 2022-11-29 /pmc/articles/PMC9726247/ /pubmed/36483984 http://dx.doi.org/10.1155/2022/2900310 Text en Copyright © 2022 Fei Xue et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Xue, Fei
Zheng, Peihao
Liu, Rui
Feng, Shaomei
Guo, Yuelu
Shi, Hui
Liu, Haidi
Deng, Biping
Xu, Teng
Ke, Xiaoyan
Hu, Kai
The Autologous Hematopoietic Stem Cells Transplantation Combination-Based Chimeric Antigen Receptor T-Cell Therapy Improves Outcomes of Relapsed/Refractory Central Nervous System B-Cell Lymphoma
title The Autologous Hematopoietic Stem Cells Transplantation Combination-Based Chimeric Antigen Receptor T-Cell Therapy Improves Outcomes of Relapsed/Refractory Central Nervous System B-Cell Lymphoma
title_full The Autologous Hematopoietic Stem Cells Transplantation Combination-Based Chimeric Antigen Receptor T-Cell Therapy Improves Outcomes of Relapsed/Refractory Central Nervous System B-Cell Lymphoma
title_fullStr The Autologous Hematopoietic Stem Cells Transplantation Combination-Based Chimeric Antigen Receptor T-Cell Therapy Improves Outcomes of Relapsed/Refractory Central Nervous System B-Cell Lymphoma
title_full_unstemmed The Autologous Hematopoietic Stem Cells Transplantation Combination-Based Chimeric Antigen Receptor T-Cell Therapy Improves Outcomes of Relapsed/Refractory Central Nervous System B-Cell Lymphoma
title_short The Autologous Hematopoietic Stem Cells Transplantation Combination-Based Chimeric Antigen Receptor T-Cell Therapy Improves Outcomes of Relapsed/Refractory Central Nervous System B-Cell Lymphoma
title_sort autologous hematopoietic stem cells transplantation combination-based chimeric antigen receptor t-cell therapy improves outcomes of relapsed/refractory central nervous system b-cell lymphoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9726247/
https://www.ncbi.nlm.nih.gov/pubmed/36483984
http://dx.doi.org/10.1155/2022/2900310
work_keys_str_mv AT xuefei theautologoushematopoieticstemcellstransplantationcombinationbasedchimericantigenreceptortcelltherapyimprovesoutcomesofrelapsedrefractorycentralnervoussystembcelllymphoma
AT zhengpeihao theautologoushematopoieticstemcellstransplantationcombinationbasedchimericantigenreceptortcelltherapyimprovesoutcomesofrelapsedrefractorycentralnervoussystembcelllymphoma
AT liurui theautologoushematopoieticstemcellstransplantationcombinationbasedchimericantigenreceptortcelltherapyimprovesoutcomesofrelapsedrefractorycentralnervoussystembcelllymphoma
AT fengshaomei theautologoushematopoieticstemcellstransplantationcombinationbasedchimericantigenreceptortcelltherapyimprovesoutcomesofrelapsedrefractorycentralnervoussystembcelllymphoma
AT guoyuelu theautologoushematopoieticstemcellstransplantationcombinationbasedchimericantigenreceptortcelltherapyimprovesoutcomesofrelapsedrefractorycentralnervoussystembcelllymphoma
AT shihui theautologoushematopoieticstemcellstransplantationcombinationbasedchimericantigenreceptortcelltherapyimprovesoutcomesofrelapsedrefractorycentralnervoussystembcelllymphoma
AT liuhaidi theautologoushematopoieticstemcellstransplantationcombinationbasedchimericantigenreceptortcelltherapyimprovesoutcomesofrelapsedrefractorycentralnervoussystembcelllymphoma
AT dengbiping theautologoushematopoieticstemcellstransplantationcombinationbasedchimericantigenreceptortcelltherapyimprovesoutcomesofrelapsedrefractorycentralnervoussystembcelllymphoma
AT xuteng theautologoushematopoieticstemcellstransplantationcombinationbasedchimericantigenreceptortcelltherapyimprovesoutcomesofrelapsedrefractorycentralnervoussystembcelllymphoma
AT kexiaoyan theautologoushematopoieticstemcellstransplantationcombinationbasedchimericantigenreceptortcelltherapyimprovesoutcomesofrelapsedrefractorycentralnervoussystembcelllymphoma
AT hukai theautologoushematopoieticstemcellstransplantationcombinationbasedchimericantigenreceptortcelltherapyimprovesoutcomesofrelapsedrefractorycentralnervoussystembcelllymphoma
AT xuefei autologoushematopoieticstemcellstransplantationcombinationbasedchimericantigenreceptortcelltherapyimprovesoutcomesofrelapsedrefractorycentralnervoussystembcelllymphoma
AT zhengpeihao autologoushematopoieticstemcellstransplantationcombinationbasedchimericantigenreceptortcelltherapyimprovesoutcomesofrelapsedrefractorycentralnervoussystembcelllymphoma
AT liurui autologoushematopoieticstemcellstransplantationcombinationbasedchimericantigenreceptortcelltherapyimprovesoutcomesofrelapsedrefractorycentralnervoussystembcelllymphoma
AT fengshaomei autologoushematopoieticstemcellstransplantationcombinationbasedchimericantigenreceptortcelltherapyimprovesoutcomesofrelapsedrefractorycentralnervoussystembcelllymphoma
AT guoyuelu autologoushematopoieticstemcellstransplantationcombinationbasedchimericantigenreceptortcelltherapyimprovesoutcomesofrelapsedrefractorycentralnervoussystembcelllymphoma
AT shihui autologoushematopoieticstemcellstransplantationcombinationbasedchimericantigenreceptortcelltherapyimprovesoutcomesofrelapsedrefractorycentralnervoussystembcelllymphoma
AT liuhaidi autologoushematopoieticstemcellstransplantationcombinationbasedchimericantigenreceptortcelltherapyimprovesoutcomesofrelapsedrefractorycentralnervoussystembcelllymphoma
AT dengbiping autologoushematopoieticstemcellstransplantationcombinationbasedchimericantigenreceptortcelltherapyimprovesoutcomesofrelapsedrefractorycentralnervoussystembcelllymphoma
AT xuteng autologoushematopoieticstemcellstransplantationcombinationbasedchimericantigenreceptortcelltherapyimprovesoutcomesofrelapsedrefractorycentralnervoussystembcelllymphoma
AT kexiaoyan autologoushematopoieticstemcellstransplantationcombinationbasedchimericantigenreceptortcelltherapyimprovesoutcomesofrelapsedrefractorycentralnervoussystembcelllymphoma
AT hukai autologoushematopoieticstemcellstransplantationcombinationbasedchimericantigenreceptortcelltherapyimprovesoutcomesofrelapsedrefractorycentralnervoussystembcelllymphoma