Frontiers in Oncology (May 2021)
A Prospective Investigation of Bispecific CD19/22 CAR T Cell Therapy in Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma
- Ying Zhang,
- Ying Zhang,
- Ying Zhang,
- Jiaqi Li,
- Jiaqi Li,
- Jiaqi Li,
- Xiaoyan Lou,
- Xiaochen Chen,
- Xiaochen Chen,
- Xiaochen Chen,
- Zhou Yu,
- Liqing Kang,
- Jia Chen,
- Jia Chen,
- Jia Chen,
- Jin Zhou,
- Jin Zhou,
- Jin Zhou,
- Xiangping Zong,
- Xiangping Zong,
- Xiangping Zong,
- Zhen Yang,
- Zhen Yang,
- Zhen Yang,
- Minghao Li,
- Nan Xu,
- Sixun Jia,
- Sixun Jia,
- Sixun Jia,
- Hongzhi Geng,
- Hongzhi Geng,
- Hongzhi Geng,
- Guanghua Chen,
- Guanghua Chen,
- Guanghua Chen,
- Haiping Dai,
- Haiping Dai,
- Haiping Dai,
- Xiaowen Tang,
- Xiaowen Tang,
- Xiaowen Tang,
- Lei Yu,
- Lei Yu,
- Depei Wu,
- Depei Wu,
- Depei Wu,
- Caixia Li,
- Caixia Li,
- Caixia Li
Affiliations
- Ying Zhang
- Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Ying Zhang
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Ying Zhang
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Jiaqi Li
- Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Jiaqi Li
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Jiaqi Li
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Xiaoyan Lou
- Shanghai Unicar-Therapy Bio-medicine Technology Co., Ltd, Shanghai, China
- Xiaochen Chen
- Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Xiaochen Chen
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Xiaochen Chen
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Zhou Yu
- Shanghai Unicar-Therapy Bio-medicine Technology Co., Ltd, Shanghai, China
- Liqing Kang
- Shanghai Unicar-Therapy Bio-medicine Technology Co., Ltd, Shanghai, China
- Jia Chen
- Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Jia Chen
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Jia Chen
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Jin Zhou
- Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Jin Zhou
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Jin Zhou
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Xiangping Zong
- Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Xiangping Zong
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Xiangping Zong
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Zhen Yang
- Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Zhen Yang
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Zhen Yang
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Minghao Li
- 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, Shanghai, China
- Nan Xu
- 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, Shanghai, China
- Sixun Jia
- Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Sixun Jia
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Sixun Jia
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Hongzhi Geng
- Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Hongzhi Geng
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Hongzhi Geng
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Guanghua Chen
- Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Guanghua Chen
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Guanghua Chen
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Haiping Dai
- Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Haiping Dai
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Haiping Dai
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Xiaowen Tang
- Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Xiaowen Tang
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Xiaowen Tang
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Lei Yu
- Shanghai Unicar-Therapy Bio-medicine Technology Co., Ltd, Shanghai, China
- Lei Yu
- 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, Shanghai, China
- Depei Wu
- Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Depei Wu
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Depei Wu
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Caixia Li
- Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Caixia Li
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Caixia Li
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- DOI
- https://doi.org/10.3389/fonc.2021.664421
- Journal volume & issue
-
Vol. 11
Abstract
BackgroundThe use of T cells expressing chimeric antigen receptor (CAR T) engineered to target CD19 constitutes breakthrough treatment for relapsed or refractory B cell non-Hodgkin lymphoma (R/R B-NHL). Despite improved outcomes, high relapse rate remains a challenge to overcome. Here, we report the clinical results and the pharmacokinetics of bispecific CD19/22 CAR T in patients with R/R B-NHL.MethodsWe performed a prospective, single-arm study of bispecific CD19/22 CAR T cells in R/R B-NHL. We analyzed the safety and efficacy and investigated the kinetic profiles of the CAR T cells. CAR transgene levels were measured using quantitative polymerase chain reaction, and correlation analyses of pharmacodynamic markers and product characteristics, disease conditions, clinical efficacy and adverse events were performed.ResultsFrom August 2017 to September 2020, a total of 32 patients with CD19/22 CAR T administration were analyzed. The overall response rate was 79.3%, and the complete response rate was 34.5%. The progression-free survival (PFS) and overall survival (OS) rates at 12 months were 40.0% and 63.3%, respectively. Among patients who had a CR at 3 months, the PFS and OS rates at 12 months were 66.7% and 100%, respectively. Severe cytokine release syndrome (sCRS) (grade 3 and higher) occurred in nine patients (28.1%). Grade 3 or higher neurologic events occurred in four patients (12.5%). One patient died from irreversible severe CRS-associated acute kidney injury. Long-term CAR T cells persistence correlated with clinical efficacy (133 days vs 22 days, P = 0.004). Patients treated with more than three prior therapies and presenting extranodal organ involvement had lower maximal concentration (Cmax) values than other patients. Responders had higher Cmax and area under the curve values than non-responders. Tumour burden and Cmax were potentially associated with the severity of CRS.ConclusionsThis study demonstrates the safety and potential clinical efficacy of bispecific CD19/22 CAR T cells in patients with R/R B-NHL and highlights the importance of measuring kinetic parameters in PB to predict efficacy and safety in clinical applications of CAR T cell therapy.Clinical Trial Registrationhttps://www.clinicaltrials.gov/ct2/show/NCT03196830, identifier NCT03196830.
Keywords
- bispecific chimeric antigen receptor
- CD19/22
- relapsed or refractory
- B cell non-Hodgkin lymphoma
- cellular kinetics
