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

IF 3.3 4区医学 Q2 HEMATOLOGY

Hematological Oncology Pub Date : 2023-09-30 DOI:10.1002/hon.3227

Ying Zhang, Hongzhi Geng, Liangyu Zeng, Jiaqi Li, Qin Yang, Sixun Jia, Xiangping Zong, Wenzhi Cai, Shuangzhu Liu, Yutong Lu, Lei Yu, Caixia Li, Depei Wu

{"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","authors":"Ying Zhang, Hongzhi Geng, Liangyu Zeng, Jiaqi Li, Qin Yang, Sixun Jia, Xiangping Zong, Wenzhi Cai, Shuangzhu Liu, Yutong Lu, Lei Yu, Caixia Li, Depei Wu","doi":"10.1002/hon.3227","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hematological Oncology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/hon.3227","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

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.

查看原文本刊更多论文

Tislelizumab增强CD19/22双靶向嵌合抗原受体T细胞在晚期复发或难治性B细胞非霍奇金淋巴瘤中的疗效。

双靶向嵌合抗原受体T（CAR-T）细胞是提高CD19 CAR-T细胞对难治性或复发性B细胞非霍奇金淋巴瘤（R/R B-NHL）疗效的重要策略。然而，在大多数患者中没有实现持久的反应，部分原因是PD-1/PD-L1途径引起的CAR-T细胞耗竭。我们在R/R B-NHL（NCT04539444）中对双靶向CD19/22 CAR-T细胞与抗PD-1抗体tislelizumab联合进行了前瞻性单臂研究。Tislelizumab在患者输注CD19/22 CAR-T细胞后+1天给药。评估了反应、存活率和安全性。从2020年8月1日至2023年3月30日，共有16名患者入选。中位随访时间为16.0个月（范围：5.0-32.0个月）。16名患者中有14名（87.5%）患者获得总体缓解，16名患者有11名（68.8%）患者获得完全缓解。1年无进展生存率和总生存率分别为68.8%和81.3%。在14名有反应的患者中，有9名患者一直保持他们的反应，直到随访结束。在16名结外受累患者中的15名（93.8%）患者中，14名（93.3%）患者达到总有效率，11名（73.3%）患者实现CR。8名（50%）患者出现细胞因子释放综合征。未报告神经系统不良事件。基因本体论生物过程富集分析表明，CR患者的免疫反应相关信号通路富集。我们的研究结果表明，CD19/22 CAR-T细胞与替斯利珠单抗联合治疗R/R B-NHL可引发安全持久的反应，并可能改善这些患者的预后。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Hematological Oncology 医学-血液学

CiteScore

4.20

自引率

6.10%

发文量

147

审稿时长

>12 weeks

期刊介绍： Hematological Oncology considers for publication articles dealing with experimental and clinical aspects of neoplastic diseases of the hemopoietic and lymphoid systems and relevant related matters. Translational studies applying basic science to clinical issues are particularly welcomed. Manuscripts dealing with the following areas are encouraged: -Clinical practice and management of hematological neoplasia, including: acute and chronic leukemias, malignant lymphomas, myeloproliferative disorders -Diagnostic investigations, including imaging and laboratory assays -Epidemiology, pathology and pathobiology of hematological neoplasia of hematological diseases -Therapeutic issues including Phase 1, 2 or 3 trials as well as allogeneic and autologous stem cell transplantation studies -Aspects of the cell biology, molecular biology, molecular genetics and cytogenetics of normal or diseased hematopoeisis and lymphopoiesis, including stem cells and cytokines and other regulatory systems. Concise, topical review material is welcomed, especially if it makes new concepts and ideas accessible to a wider community. Proposals for review material may be discussed with the Editor-in-Chief. Collections of case material and case reports will be considered only if they have broader scientific or clinical relevance.