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The differential effects of tumor burdens on predicting the net benefits of ssCART-19 cell treatment on r/r B-ALL patients.
Li, Minghao; Xue, Sheng-Li; Tang, Xiaowen; Xu, Jiayu; Chen, Suning; Han, Yue; Qiu, Huiying; Miao, Miao; Xu, Nan; Tan, Jingwen; Kang, Liqing; Yu, Zhou; Lou, Xiaoyan; Xu, Yang; Chen, Jia; Yan, Zhiqiang; Feng, Weixing; Wu, Depei; Yu, Lei.
Affiliation
  • Li M; Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, NO, 3663 North Zhongshan Road, Shanghai, 200065, China.
  • Xue SL; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.
  • Tang X; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
  • Xu J; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.
  • Chen S; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
  • Han Y; Institute of Intelligent System and Bioinformatics, College of Intelligent Systems Science and Engineering, Harbin Engineering University, Harbin, 150001, Heilongjiang, China.
  • Qiu H; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.
  • Miao M; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
  • Xu N; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.
  • Tan J; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
  • Kang L; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.
  • Yu Z; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
  • Lou X; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.
  • Xu Y; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
  • Chen J; Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, NO, 3663 North Zhongshan Road, Shanghai, 200065, China.
  • Yan Z; Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, NO, 3663 North Zhongshan Road, Shanghai, 200065, China.
  • Feng W; Shanghai Unicar-Therapy Bio-Medicine Technology Co., Ltd, No 1525 Minqiang Road, Shanghai, 201612, China.
  • Wu D; Shanghai Unicar-Therapy Bio-Medicine Technology Co., Ltd, No 1525 Minqiang Road, Shanghai, 201612, China.
  • Yu L; Shanghai Unicar-Therapy Bio-Medicine Technology Co., Ltd, No 1525 Minqiang Road, Shanghai, 201612, China.
Sci Rep ; 12(1): 378, 2022 01 10.
Article in En | MEDLINE | ID: mdl-35013456
The tumor burden (TB) is significantly related to the severity of cytokine release syndrome (CRS) caused by CAR-T cells, but its correlation with therapeutic efficacy has not been systematically studied. This study focused on the effects of the TB level on both the safety and efficacy of ssCART-19 as a treatment for r/r B-ALL. Taking the 5% tumor burden as the boundary, the study participants were divided into 2 groups, high and low tumor burden groups. Under this grouping strategy, the impacts of differential r/r B-ALL TBs on the clinical therapeutic efficacy (CR rate and long-term survival) and safety profiles after ssCART-19 cell treatment were analysed. 78 patients were reported in this study. The differential B-ALL TBs significantly affected the complete remission (CR) rates of patients treated with ssCART-19, with rates of 93.94% and 75.56% in the low and high TB groups, respectively (P = 0.0358). The effects of TBs on long-term therapeutic efficacy were further studied based on event-free survival (EFS) and overall survival (OS) profiles; both the OS and EFS of the low TB group were better than those of the high TB group, but the differences were not statistically significant. Importantly, the time points of TB measurement did not significantly affect the OS and EFS profiles regardless of whether the TBs were measured before or after fludarabine-cyclophosphamide (FC) preconditional chemotherapy. On the other hand, the severity of CRS was significantly correlated with the TB level (P = 0.0080), and the incidence of sCRS was significantly related to the TB level (the sCRS incidence increased as the TB level increased, P = 0.0224). Unexpectedly, the ssCART-19 cell expansion peaks were not significantly different (P = 0.2951) between the study groups. Patients with a low r/r B-ALL TB yield more net benefits from CAR-T treatment than those with a high TB in terms of safety and CR rate. These findings are critical and valuable for determining the optimal CAR-T cell treatment window for r/r B-ALL patients and will further the development of comprehensive and reasonable CAR-T cell treatment plans for r/r B-ALL patients with differential TBs.Trial registration: ClinicalTrials.gov identifier, NCT03919240.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: T-Lymphocytes / Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Immunotherapy, Adoptive / Receptors, Chimeric Antigen Type of study: Etiology_studies / Prognostic_studies / Risk_factors_studies Limits: Adolescent / Adult / Aged / Child / Female / Humans / Male / Middle aged Country/Region as subject: Asia Language: En Journal: Sci Rep Year: 2022 Document type: Article Affiliation country: China Country of publication: United kingdom

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: T-Lymphocytes / Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Immunotherapy, Adoptive / Receptors, Chimeric Antigen Type of study: Etiology_studies / Prognostic_studies / Risk_factors_studies Limits: Adolescent / Adult / Aged / Child / Female / Humans / Male / Middle aged Country/Region as subject: Asia Language: En Journal: Sci Rep Year: 2022 Document type: Article Affiliation country: China Country of publication: United kingdom