Prominent efficacy and good safety of sequential CD19 and CD22 CAR-T therapy in relapsed/refractory adult B-cell acute lymphoblastic leukemia
Abstract Background Sequential CD19 and CD22 chimeric antigen receptor (CAR)-T cell therapy offers a promising approach to antigen-loss relapse in relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL); however, research in adults remains limited. Methods This study aimed to evaluate...
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BMC
2025-01-01
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| Series: | Experimental Hematology & Oncology |
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| Online Access: | https://doi.org/10.1186/s40164-024-00593-5 |
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| author | Tingting Yang Yetian Dong Mingming Zhang Jingjing Feng Shan Fu Pingnan Xiao Ruimin Hong Huijun Xu Jiazhen Cui Simao Huang Guoqing Wei Delin Kong Jia Geng Alex H. Chang He Huang Yongxian Hu |
| author_facet | Tingting Yang Yetian Dong Mingming Zhang Jingjing Feng Shan Fu Pingnan Xiao Ruimin Hong Huijun Xu Jiazhen Cui Simao Huang Guoqing Wei Delin Kong Jia Geng Alex H. Chang He Huang Yongxian Hu |
| author_sort | Tingting Yang |
| collection | DOAJ |
| description | Abstract Background Sequential CD19 and CD22 chimeric antigen receptor (CAR)-T cell therapy offers a promising approach to antigen-loss relapse in relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL); however, research in adults remains limited. Methods This study aimed to evaluate the efficacy and safety of sequential CD19 and CD22 CAR-T cell therapy in adult patients with R/R B-ALL between November 2020 and November 2023 (ChiCTR2100053871). Key endpoints included the adverse event incidence, overall survival (OS), and leukemia-free survival (LFS). Results Twenty-three patients with a median age of 58.1 years (range 25.9–75.0) were enrolled. High-risk cytogenetic and genomic aberrations were identified in 43.5% of patients, and five patients had baseline extramedullary disease (EMD). The median interval between the two infusions was 3.8 months. Grade ≥ 3 hematological adverse events occurred at comparable rates after both infusions. Cytokine release syndrome was observed in 78.3% and 39.1% of patients after CD19 and CD22 CAR-T therapy, respectively. Two patients experienced grade 2 immune effector cell-associated neurotoxicity syndrome (ICANS) during CD19 CAR-T, and no ICANS was reported during CD22 CAR-T. The median OS was not reached with a median follow-up of 19.4 months (range 8.7–45.6), while the median LFS was 20.8 months. OS and LFS rates were 91.3% and 67.1% at 1 year and 58.6% and 47.0% at 2 years, respectively. Eight patients experienced relapse, with the cumulative incidence of relapse being 28.6% at 1 year and 42.5% at 2 years. Higher baseline leukemia burden (≥ 64% bone marrow blasts) and the presence of EMD were significant risk factors for inferior OS and LFS, respectively. Conclusions Sequential CAR-T cell therapy demonstrated durable efficacy and a manageable safety profile in R/R B-ALL, providing a viable option to address antigen-loss relapse and improve long-term outcomes in high-risk adult patients. |
| format | Article |
| id | doaj-art-4115bdab6d0d45b0badefdb051b0f1ec |
| institution | Kabale University |
| issn | 2162-3619 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | Experimental Hematology & Oncology |
| spelling | doaj-art-4115bdab6d0d45b0badefdb051b0f1ec2025-01-05T12:10:45ZengBMCExperimental Hematology & Oncology2162-36192025-01-0114111110.1186/s40164-024-00593-5Prominent efficacy and good safety of sequential CD19 and CD22 CAR-T therapy in relapsed/refractory adult B-cell acute lymphoblastic leukemiaTingting Yang0Yetian Dong1Mingming Zhang2Jingjing Feng3Shan Fu4Pingnan Xiao5Ruimin Hong6Huijun Xu7Jiazhen Cui8Simao Huang9Guoqing Wei10Delin Kong11Jia Geng12Alex H. Chang13He Huang14Yongxian Hu15Bone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of MedicineBone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of MedicineBone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of MedicineBone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of MedicineBone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of MedicineBone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of MedicineBone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of MedicineBone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of MedicineBone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of MedicineBone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of MedicineBone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of MedicineBone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of MedicineDepartment of Radiology of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of MedicineEngineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Fudan UniversityBone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of MedicineBone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of MedicineAbstract Background Sequential CD19 and CD22 chimeric antigen receptor (CAR)-T cell therapy offers a promising approach to antigen-loss relapse in relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL); however, research in adults remains limited. Methods This study aimed to evaluate the efficacy and safety of sequential CD19 and CD22 CAR-T cell therapy in adult patients with R/R B-ALL between November 2020 and November 2023 (ChiCTR2100053871). Key endpoints included the adverse event incidence, overall survival (OS), and leukemia-free survival (LFS). Results Twenty-three patients with a median age of 58.1 years (range 25.9–75.0) were enrolled. High-risk cytogenetic and genomic aberrations were identified in 43.5% of patients, and five patients had baseline extramedullary disease (EMD). The median interval between the two infusions was 3.8 months. Grade ≥ 3 hematological adverse events occurred at comparable rates after both infusions. Cytokine release syndrome was observed in 78.3% and 39.1% of patients after CD19 and CD22 CAR-T therapy, respectively. Two patients experienced grade 2 immune effector cell-associated neurotoxicity syndrome (ICANS) during CD19 CAR-T, and no ICANS was reported during CD22 CAR-T. The median OS was not reached with a median follow-up of 19.4 months (range 8.7–45.6), while the median LFS was 20.8 months. OS and LFS rates were 91.3% and 67.1% at 1 year and 58.6% and 47.0% at 2 years, respectively. Eight patients experienced relapse, with the cumulative incidence of relapse being 28.6% at 1 year and 42.5% at 2 years. Higher baseline leukemia burden (≥ 64% bone marrow blasts) and the presence of EMD were significant risk factors for inferior OS and LFS, respectively. Conclusions Sequential CAR-T cell therapy demonstrated durable efficacy and a manageable safety profile in R/R B-ALL, providing a viable option to address antigen-loss relapse and improve long-term outcomes in high-risk adult patients.https://doi.org/10.1186/s40164-024-00593-5Relapsed/refractory B-cell acute lymphoblastic leukemiaChimeric antigen receptorSequential therapy |
| spellingShingle | Tingting Yang Yetian Dong Mingming Zhang Jingjing Feng Shan Fu Pingnan Xiao Ruimin Hong Huijun Xu Jiazhen Cui Simao Huang Guoqing Wei Delin Kong Jia Geng Alex H. Chang He Huang Yongxian Hu Prominent efficacy and good safety of sequential CD19 and CD22 CAR-T therapy in relapsed/refractory adult B-cell acute lymphoblastic leukemia Experimental Hematology & Oncology Relapsed/refractory B-cell acute lymphoblastic leukemia Chimeric antigen receptor Sequential therapy |
| title | Prominent efficacy and good safety of sequential CD19 and CD22 CAR-T therapy in relapsed/refractory adult B-cell acute lymphoblastic leukemia |
| title_full | Prominent efficacy and good safety of sequential CD19 and CD22 CAR-T therapy in relapsed/refractory adult B-cell acute lymphoblastic leukemia |
| title_fullStr | Prominent efficacy and good safety of sequential CD19 and CD22 CAR-T therapy in relapsed/refractory adult B-cell acute lymphoblastic leukemia |
| title_full_unstemmed | Prominent efficacy and good safety of sequential CD19 and CD22 CAR-T therapy in relapsed/refractory adult B-cell acute lymphoblastic leukemia |
| title_short | Prominent efficacy and good safety of sequential CD19 and CD22 CAR-T therapy in relapsed/refractory adult B-cell acute lymphoblastic leukemia |
| title_sort | prominent efficacy and good safety of sequential cd19 and cd22 car t therapy in relapsed refractory adult b cell acute lymphoblastic leukemia |
| topic | Relapsed/refractory B-cell acute lymphoblastic leukemia Chimeric antigen receptor Sequential therapy |
| url | https://doi.org/10.1186/s40164-024-00593-5 |
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