Frontiers in Immunology (Mar 2022)
Identification of the Predictive Models for the Treatment Response of Refractory/Relapsed B-Cell ALL Patients Receiving CAR-T Therapy
- Jingxian Gu,
- Jingxian Gu,
- Jingxian Gu,
- Sining Liu,
- Sining Liu,
- Sining Liu,
- Wei Cui,
- Wei Cui,
- Wei Cui,
- Haiping Dai,
- Haiping Dai,
- Haiping Dai,
- Qingya Cui,
- Qingya Cui,
- Qingya Cui,
- Jia Yin,
- Jia Yin,
- Jia Yin,
- Zheng Li,
- Zheng Li,
- Zheng Li,
- Liqing Kang,
- Huiying Qiu,
- Huiying Qiu,
- Huiying Qiu,
- Yue Han,
- Yue Han,
- Yue Han,
- Miao Miao,
- Miao Miao,
- Miao Miao,
- Suning Chen,
- Suning Chen,
- Suning Chen,
- Shengli Xue,
- Shengli Xue,
- Shengli Xue,
- Ying Wang,
- Ying Wang,
- Ying Wang,
- Zhengming Jin,
- Zhengming Jin,
- Zhengming Jin,
- Xiaming Zhu,
- Xiaming Zhu,
- Xiaming Zhu,
- Lei Yu,
- Depei Wu,
- Depei Wu,
- Depei Wu,
- Xiaowen Tang,
- Xiaowen Tang,
- Xiaowen Tang
Affiliations
- Jingxian Gu
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Jingxian Gu
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Jingxian Gu
- Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Institute of Blood and Marrow Transplantation, Suzhou, China
- Sining Liu
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Sining Liu
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Sining Liu
- Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Institute of Blood and Marrow Transplantation, Suzhou, China
- Wei Cui
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Wei Cui
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Wei Cui
- Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Institute of Blood and Marrow Transplantation, 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
- Haiping Dai
- Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Institute of Blood and Marrow Transplantation, Suzhou, China
- Qingya Cui
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Qingya Cui
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Qingya Cui
- Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Institute of Blood and Marrow Transplantation, Suzhou, China
- Jia Yin
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Jia Yin
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Jia Yin
- Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Institute of Blood and Marrow Transplantation, Suzhou, China
- Zheng Li
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Zheng Li
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Zheng Li
- Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Institute of Blood and Marrow Transplantation, Suzhou, China
- Liqing Kang
- Research and Development Department, Shanghai Unicar-Therapy Bio-Medicine Technology Co., Ltd., Shanghai, China
- Huiying Qiu
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Huiying Qiu
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Huiying Qiu
- Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Institute of Blood and Marrow Transplantation, Suzhou, China
- Yue Han
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Yue Han
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Yue Han
- Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Institute of Blood and Marrow Transplantation, Suzhou, China
- Miao Miao
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Miao Miao
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Miao Miao
- Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Institute of Blood and Marrow Transplantation, Suzhou, China
- Suning Chen
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Suning Chen
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Suning Chen
- Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Institute of Blood and Marrow Transplantation, Suzhou, China
- Shengli Xue
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Shengli Xue
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Shengli Xue
- Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Institute of Blood and Marrow Transplantation, Suzhou, China
- Ying Wang
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Ying Wang
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Ying Wang
- Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Institute of Blood and Marrow Transplantation, Suzhou, China
- Zhengming Jin
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Zhengming Jin
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Zhengming Jin
- Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Institute of Blood and Marrow Transplantation, Suzhou, China
- Xiaming Zhu
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Xiaming Zhu
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Xiaming Zhu
- Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Institute of Blood and Marrow Transplantation, Suzhou, China
- Lei Yu
- Research and Development Department, Shanghai Unicar-Therapy Bio-Medicine Technology Co., Ltd., Shanghai, 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
- Depei Wu
- Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Institute of Blood and Marrow Transplantation, 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
- Xiaowen Tang
- Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Institute of Blood and Marrow Transplantation, Suzhou, China
- DOI
- https://doi.org/10.3389/fimmu.2022.858590
- Journal volume & issue
-
Vol. 13
Abstract
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.
Keywords
- chimeric antigen receptor T cells
- refractory or relapsed B-cell acute lymphoblastic leukemia
- predictive models
- complete remission
- MRD-negative complete remission