{"title":"CNCT19嵌合抗原受体t细胞治疗复发或难治性侵袭性b细胞淋巴瘤的长期疗效","authors":"Wei Liu, Ting Xie, Zhuoxin Zhang, Wenyang Huang, Huimin Liu, Weiwei Sui, Shuhui Deng, Rui Lv, Yi Wang, Qi Wang, Wenjie Xiong, Yan Xu, Lulu Lv, Yueshen Ma, Lugui Qiu, Jianxiang Wang, Dehui Zou","doi":"10.1097/CM9.0000000000003716","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Most anti-CD19 chimeric antigen receptor (CAR) T-cell products have the single-chain variable fragment (scFv) derived from the FMC63 monoclonal antibody. We developed a new hybridoma clone, HI19α, which binds to distinct epitopes on CD19. CNCT19 is a second-generation CAR T-cell with a scFv derived from clone HI19α and a 4-1BB costimulatory domain. A pilot clinical trial was conducted to assess the safety and preliminary efficacy of CNCT19 cells (CNCT19s) in patients with relapsed or refractory (R/R) aggressive B-cell lymphoma.</p><p><strong>Methods: </strong>From June 2017 to March 2019, 16 patients with R/R CD19-positive aggressive B-cell lymphoma from the Institute of Hematology and Blood Disease Hospital were enrolled. All patients received lymphodepleting chemotherapy with fludarabine (25-30 mg/m2/per day on days 4, 3, and 2) and cyclophosphamide (350 mg/m2/per day on days 4 and 2) before CNCT19s infusion. The primary objective was the safety profiles. Kaplan-Meier survival analysis was used to compare the cumulative incidence rate.</p><p><strong>Results: </strong>The study cohort comprised 14 patients diagnosed with de novo diffuse large B-cell lymphoma (DLBCL), one patient with follicular lymphoma grade 3B (FL3B), and one patient with Richter's transformation. The patients had received a median of 3 (range 1-7) lines of prior therapy. Thirteen patients (81.3%) had disease resistant to the last-line therapy, and TP53 mutation and/or deletion were detected in 5 of 12 patients (41.7%). The median dose of CNCT19s infusion was 3.6 × 106 (range 1.8-6.5 × 106)/kg. Cytokine release syndrome occurred in 11 (68.8%) patients, all classified as grade 1. One patient (6.3%) experienced CAR T-cell-related encephalopathy syndrome. The overall response rate and the complete response rate were 75% (12/16) and 43.8% (7/16), respectively. After a median follow-up of 54.0 months, the estimated 5-year progression-free survival and overall survival rates were 25.0% and 37.5%, respectively.</p><p><strong>Conclusions: </strong>CNCT19s exhibited favorable safety profiles and efficacy in patients with R/R DLBCL and FL3B. Long-term follow-up confirmed the curative potential of CNCT19s in R/R aggressive B-cell lymphoma.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT03029338.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.3000,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Long-term outcomes of CNCT19 chimeric antigen receptor T-cell therapy in relapsed or refractory aggressive B-cell lymphoma.\",\"authors\":\"Wei Liu, Ting Xie, Zhuoxin Zhang, Wenyang Huang, Huimin Liu, Weiwei Sui, Shuhui Deng, Rui Lv, Yi Wang, Qi Wang, Wenjie Xiong, Yan Xu, Lulu Lv, Yueshen Ma, Lugui Qiu, Jianxiang Wang, Dehui Zou\",\"doi\":\"10.1097/CM9.0000000000003716\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Most anti-CD19 chimeric antigen receptor (CAR) T-cell products have the single-chain variable fragment (scFv) derived from the FMC63 monoclonal antibody. We developed a new hybridoma clone, HI19α, which binds to distinct epitopes on CD19. CNCT19 is a second-generation CAR T-cell with a scFv derived from clone HI19α and a 4-1BB costimulatory domain. A pilot clinical trial was conducted to assess the safety and preliminary efficacy of CNCT19 cells (CNCT19s) in patients with relapsed or refractory (R/R) aggressive B-cell lymphoma.</p><p><strong>Methods: </strong>From June 2017 to March 2019, 16 patients with R/R CD19-positive aggressive B-cell lymphoma from the Institute of Hematology and Blood Disease Hospital were enrolled. All patients received lymphodepleting chemotherapy with fludarabine (25-30 mg/m2/per day on days 4, 3, and 2) and cyclophosphamide (350 mg/m2/per day on days 4 and 2) before CNCT19s infusion. The primary objective was the safety profiles. Kaplan-Meier survival analysis was used to compare the cumulative incidence rate.</p><p><strong>Results: </strong>The study cohort comprised 14 patients diagnosed with de novo diffuse large B-cell lymphoma (DLBCL), one patient with follicular lymphoma grade 3B (FL3B), and one patient with Richter's transformation. The patients had received a median of 3 (range 1-7) lines of prior therapy. Thirteen patients (81.3%) had disease resistant to the last-line therapy, and TP53 mutation and/or deletion were detected in 5 of 12 patients (41.7%). The median dose of CNCT19s infusion was 3.6 × 106 (range 1.8-6.5 × 106)/kg. Cytokine release syndrome occurred in 11 (68.8%) patients, all classified as grade 1. One patient (6.3%) experienced CAR T-cell-related encephalopathy syndrome. The overall response rate and the complete response rate were 75% (12/16) and 43.8% (7/16), respectively. After a median follow-up of 54.0 months, the estimated 5-year progression-free survival and overall survival rates were 25.0% and 37.5%, respectively.</p><p><strong>Conclusions: </strong>CNCT19s exhibited favorable safety profiles and efficacy in patients with R/R DLBCL and FL3B. Long-term follow-up confirmed the curative potential of CNCT19s in R/R aggressive B-cell lymphoma.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT03029338.</p>\",\"PeriodicalId\":10183,\"journal\":{\"name\":\"Chinese Medical Journal\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":7.3000,\"publicationDate\":\"2025-09-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chinese Medical Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/CM9.0000000000003716\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chinese Medical Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/CM9.0000000000003716","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
Long-term outcomes of CNCT19 chimeric antigen receptor T-cell therapy in relapsed or refractory aggressive B-cell lymphoma.
Background: Most anti-CD19 chimeric antigen receptor (CAR) T-cell products have the single-chain variable fragment (scFv) derived from the FMC63 monoclonal antibody. We developed a new hybridoma clone, HI19α, which binds to distinct epitopes on CD19. CNCT19 is a second-generation CAR T-cell with a scFv derived from clone HI19α and a 4-1BB costimulatory domain. A pilot clinical trial was conducted to assess the safety and preliminary efficacy of CNCT19 cells (CNCT19s) in patients with relapsed or refractory (R/R) aggressive B-cell lymphoma.
Methods: From June 2017 to March 2019, 16 patients with R/R CD19-positive aggressive B-cell lymphoma from the Institute of Hematology and Blood Disease Hospital were enrolled. All patients received lymphodepleting chemotherapy with fludarabine (25-30 mg/m2/per day on days 4, 3, and 2) and cyclophosphamide (350 mg/m2/per day on days 4 and 2) before CNCT19s infusion. The primary objective was the safety profiles. Kaplan-Meier survival analysis was used to compare the cumulative incidence rate.
Results: The study cohort comprised 14 patients diagnosed with de novo diffuse large B-cell lymphoma (DLBCL), one patient with follicular lymphoma grade 3B (FL3B), and one patient with Richter's transformation. The patients had received a median of 3 (range 1-7) lines of prior therapy. Thirteen patients (81.3%) had disease resistant to the last-line therapy, and TP53 mutation and/or deletion were detected in 5 of 12 patients (41.7%). The median dose of CNCT19s infusion was 3.6 × 106 (range 1.8-6.5 × 106)/kg. Cytokine release syndrome occurred in 11 (68.8%) patients, all classified as grade 1. One patient (6.3%) experienced CAR T-cell-related encephalopathy syndrome. The overall response rate and the complete response rate were 75% (12/16) and 43.8% (7/16), respectively. After a median follow-up of 54.0 months, the estimated 5-year progression-free survival and overall survival rates were 25.0% and 37.5%, respectively.
Conclusions: CNCT19s exhibited favorable safety profiles and efficacy in patients with R/R DLBCL and FL3B. Long-term follow-up confirmed the curative potential of CNCT19s in R/R aggressive B-cell lymphoma.
期刊介绍：
The Chinese Medical Journal (CMJ) is published semimonthly in English by the Chinese Medical Association, and is a peer reviewed general medical journal for all doctors, researchers, and health workers regardless of their medical specialty or type of employment. Established in 1887, it is the oldest medical periodical in China and is distributed worldwide. The journal functions as a window into China’s medical sciences and reflects the advances and progress in China’s medical sciences and technology. It serves the objective of international academic exchange. The journal includes Original Articles, Editorial, Review Articles, Medical Progress, Brief Reports, Case Reports, Viewpoint, Clinical Exchange, Letter,and News,etc. CMJ is abstracted or indexed in many databases including Biological Abstracts, Chemical Abstracts, Index Medicus/Medline, Science Citation Index (SCI), Current Contents, Cancerlit, Health Plan & Administration, Embase, Social Scisearch, Aidsline, Toxline, Biocommercial Abstracts, Arts and Humanities Search, Nuclear Science Abstracts, Water Resources Abstracts, Cab Abstracts, Occupation Safety & Health, etc. In 2007, the impact factor of the journal by SCI is 0.636, and the total citation is 2315.
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