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Anti-PD-1 antibodies as a salvage therapy for patients with diffuse large B cell lymphoma who progressed/relapsed after CART19/20 therapy

CD19-directed chimeric antigen receptor T cell (CART19) therapy is efficient and approved for relapsed/refractory diffuse large B cell lymphoma (DLBCL). To increase durable antitumor response, we previously designed tandem CART19/20 cells and shown longer progression-free survival. However, a propor...

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Autores principales: Wang, Chunmeng, Shi, Fengxia, Liu, Yang, Zhang, Yajing, Dong, Liang, Li, Xiang, Tong, Chuan, Wang, Yao, Su, Liping, Nie, Jing, Han, Weidong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259370/
https://www.ncbi.nlm.nih.gov/pubmed/34225766
http://dx.doi.org/10.1186/s13045-021-01120-3
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author Wang, Chunmeng
Shi, Fengxia
Liu, Yang
Zhang, Yajing
Dong, Liang
Li, Xiang
Tong, Chuan
Wang, Yao
Su, Liping
Nie, Jing
Han, Weidong
author_facet Wang, Chunmeng
Shi, Fengxia
Liu, Yang
Zhang, Yajing
Dong, Liang
Li, Xiang
Tong, Chuan
Wang, Yao
Su, Liping
Nie, Jing
Han, Weidong
author_sort Wang, Chunmeng
collection PubMed
description CD19-directed chimeric antigen receptor T cell (CART19) therapy is efficient and approved for relapsed/refractory diffuse large B cell lymphoma (DLBCL). To increase durable antitumor response, we previously designed tandem CART19/20 cells and shown longer progression-free survival. However, a proportion of CART19/20-treated patients will finally progress and require salvage therapies. In this study, we analyzed data from five patients with relapsed/refractory DLBCL who had disease progression or relapse following CART19/20 therapy and then treated with PD-1-blocking antibodies as salvage therapy. Two of five patients acquired complete remissions after anti-PD-1 therapy, including one patient remained ongoing remission for more than 21 months. One patient achieved a partial remission, and the other two had progressive diseases. No ≥ grade 3 treatment-related adverse events or cytokine release syndrome was observed. Immunohistochemistry of tumor specimens revealed higher PD-1/PD-L1 expression in responsive patients with anti-PD-1 therapy as compared to that in non-responders. After anti-PD-1 treatment, circulating T cells were activated in responders, and no significant expansion of CART19/20 cells was detected. Our data suggest that PD-1 blockade therapy can be active in patients with relapsed/refractory DLBCL after failure of CAR T cell therapy who had PD-L1 expression in tumor cells and high PD-1 level in tumor-infiltrated T cells. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13045-021-01120-3.
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spelling pubmed-82593702021-07-06 Anti-PD-1 antibodies as a salvage therapy for patients with diffuse large B cell lymphoma who progressed/relapsed after CART19/20 therapy Wang, Chunmeng Shi, Fengxia Liu, Yang Zhang, Yajing Dong, Liang Li, Xiang Tong, Chuan Wang, Yao Su, Liping Nie, Jing Han, Weidong J Hematol Oncol Letter to the Editor CD19-directed chimeric antigen receptor T cell (CART19) therapy is efficient and approved for relapsed/refractory diffuse large B cell lymphoma (DLBCL). To increase durable antitumor response, we previously designed tandem CART19/20 cells and shown longer progression-free survival. However, a proportion of CART19/20-treated patients will finally progress and require salvage therapies. In this study, we analyzed data from five patients with relapsed/refractory DLBCL who had disease progression or relapse following CART19/20 therapy and then treated with PD-1-blocking antibodies as salvage therapy. Two of five patients acquired complete remissions after anti-PD-1 therapy, including one patient remained ongoing remission for more than 21 months. One patient achieved a partial remission, and the other two had progressive diseases. No ≥ grade 3 treatment-related adverse events or cytokine release syndrome was observed. Immunohistochemistry of tumor specimens revealed higher PD-1/PD-L1 expression in responsive patients with anti-PD-1 therapy as compared to that in non-responders. After anti-PD-1 treatment, circulating T cells were activated in responders, and no significant expansion of CART19/20 cells was detected. Our data suggest that PD-1 blockade therapy can be active in patients with relapsed/refractory DLBCL after failure of CAR T cell therapy who had PD-L1 expression in tumor cells and high PD-1 level in tumor-infiltrated T cells. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13045-021-01120-3. BioMed Central 2021-07-05 /pmc/articles/PMC8259370/ /pubmed/34225766 http://dx.doi.org/10.1186/s13045-021-01120-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Letter to the Editor
Wang, Chunmeng
Shi, Fengxia
Liu, Yang
Zhang, Yajing
Dong, Liang
Li, Xiang
Tong, Chuan
Wang, Yao
Su, Liping
Nie, Jing
Han, Weidong
Anti-PD-1 antibodies as a salvage therapy for patients with diffuse large B cell lymphoma who progressed/relapsed after CART19/20 therapy
title Anti-PD-1 antibodies as a salvage therapy for patients with diffuse large B cell lymphoma who progressed/relapsed after CART19/20 therapy
title_full Anti-PD-1 antibodies as a salvage therapy for patients with diffuse large B cell lymphoma who progressed/relapsed after CART19/20 therapy
title_fullStr Anti-PD-1 antibodies as a salvage therapy for patients with diffuse large B cell lymphoma who progressed/relapsed after CART19/20 therapy
title_full_unstemmed Anti-PD-1 antibodies as a salvage therapy for patients with diffuse large B cell lymphoma who progressed/relapsed after CART19/20 therapy
title_short Anti-PD-1 antibodies as a salvage therapy for patients with diffuse large B cell lymphoma who progressed/relapsed after CART19/20 therapy
title_sort anti-pd-1 antibodies as a salvage therapy for patients with diffuse large b cell lymphoma who progressed/relapsed after cart19/20 therapy
topic Letter to the Editor
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259370/
https://www.ncbi.nlm.nih.gov/pubmed/34225766
http://dx.doi.org/10.1186/s13045-021-01120-3
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