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PiggyBac-Generated CAR19-T Cells Plus Lenalidomide Cause Durable Complete Remission of Triple-Hit Refractory/Relapsed DLBCL: A Case Report

MYC/BCL2/BCL6 triple-hit lymphoma (THL) is an uncommon subset of high-grade B-cell lymphoma with aggressive clinical behavior and poor prognosis. TP53 mutation is an independently poor progonistic indicator in patients with THL, hence novel therapeutic strategies are needed for these patients. CD19-...

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Autores principales: Li, Chenggong, Sun, Yan, Wang, Jing, Tang, Lu, Jiang, Huiwen, Guo, Tao, Liu, Lin, Wu, Yaohui, Ai, Lisha, Xia, Linghui, Wu, Jianjun, Lin, Zhicai, Qian, Qijun, Hu, Yu, Mei, Heng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186315/
https://www.ncbi.nlm.nih.gov/pubmed/34113336
http://dx.doi.org/10.3389/fimmu.2021.599493
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author Li, Chenggong
Sun, Yan
Wang, Jing
Tang, Lu
Jiang, Huiwen
Guo, Tao
Liu, Lin
Wu, Yaohui
Ai, Lisha
Xia, Linghui
Wu, Jianjun
Lin, Zhicai
Qian, Qijun
Hu, Yu
Mei, Heng
author_facet Li, Chenggong
Sun, Yan
Wang, Jing
Tang, Lu
Jiang, Huiwen
Guo, Tao
Liu, Lin
Wu, Yaohui
Ai, Lisha
Xia, Linghui
Wu, Jianjun
Lin, Zhicai
Qian, Qijun
Hu, Yu
Mei, Heng
author_sort Li, Chenggong
collection PubMed
description MYC/BCL2/BCL6 triple-hit lymphoma (THL) is an uncommon subset of high-grade B-cell lymphoma with aggressive clinical behavior and poor prognosis. TP53 mutation is an independently poor progonistic indicator in patients with THL, hence novel therapeutic strategies are needed for these patients. CD19-directed chimeric antigen receptor(CAR19)-T cell therapy has shown promising efficacy for relapsed/refractory diffuse large B cell lymphoma (RR DLBCL), but the majority of CAR19-T cell products to date have been manufactured using viral vectors. PiggyBac transposon system, with an inclination to memory T cells, offers a more convenient and economical alternative for transgene delivery. We herein report the first case of triple-hit RR DLBCL with TP53 mutation who was treated with piggyBac-generated CAR19-T cells and accompanied by grade 2 cytokine release syndrome. The patient obtained a complete remission (CR) in the 2nd month post-infusion and demanded maintenance therapy. Whether maintenance therapy is favorable and how to administrate it after CAR-T cell infusion remain controversial. Preclinical studies demonstrated that lenalidomide could enhance antitumor activity of CAR19-T cells. Therefore, we pioneered oral lenalidomide after CAR19-T therapy in the patient from the 4th month, and he discontinued after one cycle due to side effects. The patient has still kept sustained CR for over 24 months. Our case have firstly demonstrated the feasibility, preliminary safety and efficacy of piggyBac-produced CAR19-T cell therapy in triple-hit lymphoma. The innovative combination with lenalidomide warrants further investigation. Our findings shed new light on the possible solutions to improve short-term relapse after CAR19-T cell therapy in RR DLBCL. ChiCTR, number ChiCTR1800018111.
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spelling pubmed-81863152021-06-09 PiggyBac-Generated CAR19-T Cells Plus Lenalidomide Cause Durable Complete Remission of Triple-Hit Refractory/Relapsed DLBCL: A Case Report Li, Chenggong Sun, Yan Wang, Jing Tang, Lu Jiang, Huiwen Guo, Tao Liu, Lin Wu, Yaohui Ai, Lisha Xia, Linghui Wu, Jianjun Lin, Zhicai Qian, Qijun Hu, Yu Mei, Heng Front Immunol Immunology MYC/BCL2/BCL6 triple-hit lymphoma (THL) is an uncommon subset of high-grade B-cell lymphoma with aggressive clinical behavior and poor prognosis. TP53 mutation is an independently poor progonistic indicator in patients with THL, hence novel therapeutic strategies are needed for these patients. CD19-directed chimeric antigen receptor(CAR19)-T cell therapy has shown promising efficacy for relapsed/refractory diffuse large B cell lymphoma (RR DLBCL), but the majority of CAR19-T cell products to date have been manufactured using viral vectors. PiggyBac transposon system, with an inclination to memory T cells, offers a more convenient and economical alternative for transgene delivery. We herein report the first case of triple-hit RR DLBCL with TP53 mutation who was treated with piggyBac-generated CAR19-T cells and accompanied by grade 2 cytokine release syndrome. The patient obtained a complete remission (CR) in the 2nd month post-infusion and demanded maintenance therapy. Whether maintenance therapy is favorable and how to administrate it after CAR-T cell infusion remain controversial. Preclinical studies demonstrated that lenalidomide could enhance antitumor activity of CAR19-T cells. Therefore, we pioneered oral lenalidomide after CAR19-T therapy in the patient from the 4th month, and he discontinued after one cycle due to side effects. The patient has still kept sustained CR for over 24 months. Our case have firstly demonstrated the feasibility, preliminary safety and efficacy of piggyBac-produced CAR19-T cell therapy in triple-hit lymphoma. The innovative combination with lenalidomide warrants further investigation. Our findings shed new light on the possible solutions to improve short-term relapse after CAR19-T cell therapy in RR DLBCL. ChiCTR, number ChiCTR1800018111. Frontiers Media S.A. 2021-05-25 /pmc/articles/PMC8186315/ /pubmed/34113336 http://dx.doi.org/10.3389/fimmu.2021.599493 Text en Copyright © 2021 Li, Sun, Wang, Tang, Jiang, Guo, Liu, Wu, Ai, Xia, Wu, Lin, Qian, Hu and Mei https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Li, Chenggong
Sun, Yan
Wang, Jing
Tang, Lu
Jiang, Huiwen
Guo, Tao
Liu, Lin
Wu, Yaohui
Ai, Lisha
Xia, Linghui
Wu, Jianjun
Lin, Zhicai
Qian, Qijun
Hu, Yu
Mei, Heng
PiggyBac-Generated CAR19-T Cells Plus Lenalidomide Cause Durable Complete Remission of Triple-Hit Refractory/Relapsed DLBCL: A Case Report
title PiggyBac-Generated CAR19-T Cells Plus Lenalidomide Cause Durable Complete Remission of Triple-Hit Refractory/Relapsed DLBCL: A Case Report
title_full PiggyBac-Generated CAR19-T Cells Plus Lenalidomide Cause Durable Complete Remission of Triple-Hit Refractory/Relapsed DLBCL: A Case Report
title_fullStr PiggyBac-Generated CAR19-T Cells Plus Lenalidomide Cause Durable Complete Remission of Triple-Hit Refractory/Relapsed DLBCL: A Case Report
title_full_unstemmed PiggyBac-Generated CAR19-T Cells Plus Lenalidomide Cause Durable Complete Remission of Triple-Hit Refractory/Relapsed DLBCL: A Case Report
title_short PiggyBac-Generated CAR19-T Cells Plus Lenalidomide Cause Durable Complete Remission of Triple-Hit Refractory/Relapsed DLBCL: A Case Report
title_sort piggybac-generated car19-t cells plus lenalidomide cause durable complete remission of triple-hit refractory/relapsed dlbcl: a case report
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186315/
https://www.ncbi.nlm.nih.gov/pubmed/34113336
http://dx.doi.org/10.3389/fimmu.2021.599493
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