Identification of the Predictive Models for the Treatment Response of Refractory/Relapsed B-Cell ALL Patients Receiving CAR-T Therapy

Frontiers in Immunology

Sining Liu²  Huiying Qiu²  Miao Miao²  Xiaming Zhu²  Zheng Li²  Depei Wu²  Jingxian Gu²  Shengli Xue²  Yue Han²  Haiping Dai²  Zhengming Jin²  Suning Chen²  Ying Wang²  Xiaowen Tang²  Qingya Cui²  Wei Cui²  Jia Yin²  Lei Yu⁴  Liqing Kang⁴ 

[1] Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China;Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Institute of Blood and Marrow Transplantation, Suzhou, China;National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China;Research and Development Department, Shanghai Unicar-Therapy Bio-Medicine Technology Co., Ltd., Shanghai, China;

关键词: chimeric antigen receptor T cells;    refractory or relapsed B-cell acute lymphoblastic leukemia;    predictive models;    complete remission;    MRD-negative complete remission;   

DOI  :  10.3389/fimmu.2022.858590

来源: DOAJ

【 摘 要 】

Background/AimsChimeric antigen receptor (CAR) T cells for refractory or relapsed (r/r) B-cell acute lymphoblastic leukemia (ALL) patients have shown promising clinical effectiveness. However, the factors impacting the clinical response of CAR-T therapy have not been fully elucidated. We here aimed to identify the independent factors of CAR-T treatment response and construct the models for predicting the complete remission (CR) and minimal residual disease (MRD)-negative CR in r/r B-ALL patients after CAR-T cell infusion.MethodsUnivariate and multivariate logistic regression analyses were conducted to identify the independent factors of CR and MRD-negative CR. The predictive models for the probability of remission were constructed based on the identified independent factors. Discrimination and calibration of the established models were assessed by receiver operating characteristic (ROC) curves and calibration plots, respectively. The predictive models were further integrated and validated in the internal series. Moreover, the prognostic value of the integration risk model was also confirmed.ResultsThe predictive model for CR was formulated by the number of white blood cells (WBC), central neural system (CNS) leukemia, TP53 mutation, bone marrow blasts, and CAR-T cell generation while the model for MRD-negative CR was formulated by disease status, bone marrow blasts, and infusion strategy. The ROC curves and calibration plots of the two models displayed great discrimination and calibration ability. Patients and infusions were divided into different risk groups according to the integration model. High-risk groups showed significant lower CR and MRD-negative CR rates in both the training and validation sets (p < 0.01). Furthermore, low-risk patients exhibited improved overall survival (OS) (log-rank p < 0.01), higher 6-month event-free survival (EFS) rate (p < 0.01), and lower relapse rate after the allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T cell infusion (p = 0.06).ConclusionsWe have established predictive models for treatment response estimation of CAR-T therapy. Our models also provided new clinical insights for the accurate diagnosis and targeted treatment of r/r B-ALL.

【 授权许可】

Unknown