A Prospective Investigation of Bispecific CD19/22 CAR T Cell Therapy in Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma

Frontiers in Oncology

卷:11

Nan Xu¹  Lei Yu¹  Minghao Li¹  Jin Zhou²  Xiaochen Chen²  Jia Chen²  Sixun Jia²  Guanghua Chen²  Ying Zhang²  Zhen Yang²  Depei Wu²  Jiaqi Li²  Xiangping Zong²  Haiping Dai²  Caixia Li²  Hongzhi Geng²  Xiaowen Tang²  Liqing Kang⁵  Xiaoyan Lou⁵  Zhou Yu⁵ 

[1] 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;

[2] Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China;

[3] Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China;

[4] National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China;

[5] Shanghai Unicar-Therapy Bio-medicine Technology Co., Ltd, Shanghai, China;

关键词: bispecific chimeric antigen receptor;    CD19/22;    relapsed or refractory;    B cell non-Hodgkin lymphoma;    cellular kinetics;   

DOI  :  10.3389/fonc.2021.664421

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown