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Tislelizumab augment the efficacy of CD19/22 dual‐targeted chimeric antigen receptor T cell in advanced stage relapsed or refractory B‐cell non‐Hodgkin lymphoma

Dual‐targeted chimeric antigen receptor T (CAR‐T) cell is an important strategy to improve the efficacy of CD19 CAR‐T cell against refractory or relapsed B cell non‐Hodgkin lymphoma (R/R B‐NHL). However, durable responses are not achieved in most patients, in part owing CAR‐T cell exhaustion caused...

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Published in:Hematological oncology 2024-01, Vol.42 (1), p.e3227-n/a
Main Authors: Zhang, Ying, Geng, Hongzhi, Zeng, Liangyu, Li, Jiaqi, Yang, Qin, Jia, Sixun, Zong, Xiangping, Cai, Wenzhi, Liu, Shuangzhu, Lu, Yutong, Yu, Lei, Li, Caixia, Wu, Depei
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container_start_page e3227
container_title Hematological oncology
container_volume 42
creator Zhang, Ying
Geng, Hongzhi
Zeng, Liangyu
Li, Jiaqi
Yang, Qin
Jia, Sixun
Zong, Xiangping
Cai, Wenzhi
Liu, Shuangzhu
Lu, Yutong
Yu, Lei
Li, Caixia
Wu, Depei
description Dual‐targeted chimeric antigen receptor T (CAR‐T) cell is an important strategy to improve the efficacy of CD19 CAR‐T cell against refractory or relapsed B cell non‐Hodgkin lymphoma (R/R B‐NHL). However, durable responses are not achieved in most patients, in part owing CAR‐T cell exhaustion caused by PD‐1/PD‐L1 pathway. We conducted a prospective, single‐arm study of dual‐targeted CD19/22 CAR‐T cell combined with anti‐PD‐1 antibody, tislelizumab, in R/R B‐NHL (NCT04539444). Tislelizumab was administrated on +1 day after patients received infusion of CD19/22 CAR‐T cell. Responses, survival and safety were evaluated. From 1 August 2020 to 30 March 2023, 16 patients were enrolled. The median follow‐up time is 16.0 (range: 5.0–32.0 months) months. Overall response was achieved in 14 of 16 (87.5%) patients, and the complete response (CR) was achieved in 11 of 16 (68.8%) patients. The 1‐year progression‐free survival and overall survival rates were 68.8% and 81.3%, respectively. Of the 14 patients responded, 9 patients maintained their response until the end of follow‐up. Among the 15 out of 16 (93.8%) patients who had extranodal involvement, 14 (93.3%) patients achieved overall response rate with 11 (73.3%) patients achieving CR. Eight (50%) patients experienced cytokine release syndrome. No neurologic adverse events were reported. Gene Ontology‐Biological Process enrichment analysis showed that immune response‐related signaling pathways were enriched in CR patients. Our results suggest that CD19/22 CAR‐T cell combined with tislelizumab elicit a safe and durable response in R/R B‐NHL and may improve the prognosis of those patients.
doi_str_mv 10.1002/hon.3227
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However, durable responses are not achieved in most patients, in part owing CAR‐T cell exhaustion caused by PD‐1/PD‐L1 pathway. We conducted a prospective, single‐arm study of dual‐targeted CD19/22 CAR‐T cell combined with anti‐PD‐1 antibody, tislelizumab, in R/R B‐NHL (NCT04539444). Tislelizumab was administrated on +1 day after patients received infusion of CD19/22 CAR‐T cell. Responses, survival and safety were evaluated. From 1 August 2020 to 30 March 2023, 16 patients were enrolled. The median follow‐up time is 16.0 (range: 5.0–32.0 months) months. Overall response was achieved in 14 of 16 (87.5%) patients, and the complete response (CR) was achieved in 11 of 16 (68.8%) patients. The 1‐year progression‐free survival and overall survival rates were 68.8% and 81.3%, respectively. Of the 14 patients responded, 9 patients maintained their response until the end of follow‐up. 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However, durable responses are not achieved in most patients, in part owing CAR‐T cell exhaustion caused by PD‐1/PD‐L1 pathway. We conducted a prospective, single‐arm study of dual‐targeted CD19/22 CAR‐T cell combined with anti‐PD‐1 antibody, tislelizumab, in R/R B‐NHL (NCT04539444). Tislelizumab was administrated on +1 day after patients received infusion of CD19/22 CAR‐T cell. Responses, survival and safety were evaluated. From 1 August 2020 to 30 March 2023, 16 patients were enrolled. The median follow‐up time is 16.0 (range: 5.0–32.0 months) months. Overall response was achieved in 14 of 16 (87.5%) patients, and the complete response (CR) was achieved in 11 of 16 (68.8%) patients. The 1‐year progression‐free survival and overall survival rates were 68.8% and 81.3%, respectively. Of the 14 patients responded, 9 patients maintained their response until the end of follow‐up. Among the 15 out of 16 (93.8%) patients who had extranodal involvement, 14 (93.3%) patients achieved overall response rate with 11 (73.3%) patients achieving CR. Eight (50%) patients experienced cytokine release syndrome. No neurologic adverse events were reported. Gene Ontology‐Biological Process enrichment analysis showed that immune response‐related signaling pathways were enriched in CR patients. Our results suggest that CD19/22 CAR‐T cell combined with tislelizumab elicit a safe and durable response in R/R B‐NHL and may improve the prognosis of those patients.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>37776326</pmid><doi>10.1002/hon.3227</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-5480-3023</orcidid><oa>free_for_read</oa></addata></record>
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source Wiley-Blackwell Read & Publish Collection
subjects Antibodies
Antigens
anti‐PD‐1 antibody
Biological activity
CD19 antigen
CD19/CD22 chimeric antigen receptor T cell
Cell survival
Chimeric antigen receptors
Effectiveness
Immune response
Lymphocytes
Lymphocytes T
Lymphoma
Medical prognosis
Non-Hodgkin's lymphoma
PD-L1 protein
Receptors
refractory or relapsed B cell non‐Hodgkin lymphoma
Survival
tislelizumab
title Tislelizumab augment the efficacy of CD19/22 dual‐targeted chimeric antigen receptor T cell in advanced stage relapsed or refractory B‐cell non‐Hodgkin lymphoma
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