The influence of CRS and ICANS on the efficacy of anti-CD19 CAR-T treatment for B-cell acute lymphoblastic leukemia

被引:2
作者
Ma, Yuhan [1 ]
Zhou, Hongyuan [2 ,3 ]
Zhang, Jiaoli [4 ]
Zhang, Qing [2 ,3 ]
Li, Yujie [2 ,3 ]
Xie, Ruiyang [2 ,3 ]
Zhang, Bingpei [2 ,3 ]
Shen, Ziyuan [5 ]
Li, Ping [6 ]
Liang, Aibin [6 ]
Zhou, Keshu [7 ]
Han, Lu [7 ]
Hu, Yongxian [8 ]
Xu, Kailin [2 ,3 ]
Sang, Wei [2 ,3 ]
Wang, Xiangmin [2 ,3 ]
机构
[1] Suqian First Hosp, Dept Hematol, Suqian, Peoples R China
[2] Xuzhou Med Univ, Affiliated Hosp, Dept Hematol, Xuzhou, Peoples R China
[3] Xuzhou Med Univ, Blood Dis Inst, Xuzhou, Peoples R China
[4] Xuzhou Med Univ, Affiliated Hosp, Dept Rehabil, Xuzhou, Peoples R China
[5] Anhui Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Hefei, Anhui, Peoples R China
[6] Tongji Univ, Tongji Hosp, Dept Hematol, Shanghai, Peoples R China
[7] Zhengzhou Univ, Affiliated Canc Hosp, Dept Hematol, Zhengzhou, Peoples R China
[8] Zhejiang Univ, Affiliated Hosp 1, Sch Med, Dept Hematol, Hangzhou, Peoples R China
关键词
cytokine release syndrome; immune effector cell-associated neurotoxicity syndrome; chimeric antigen receptor T cell therapy; relapsed/refractory B cell lymphoblastic leukemia; efficacy; THERAPY;
D O I
10.3389/fimmu.2024.1448709
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background Chimeric antigen receptor T-cell (CAR-T) therapy has offered new opportunities for patients with relapsed/refractory B-cell lymphoblastic leukemia (r/r B-ALL). However, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are the two most common toxicities following CAR-T cell therapy. At present, whether the occurrence of CRS and ICANS will impact CAR-T activity remains unknown; this affects the therapeutic efficacy of CAR-T.Methods In this multicenter retrospective study, we enrolled 93 patients with r/r B-ALL receiving anti-CD19 CAR-T cell therapy at four medical centers. We evaluated their complete response (CR) rates, minimal residual disease (MRD)-negative CR rates, and survival outcomes.Results Among the included patients, 76 (81.7%) developed CRS and 16 (5.3%) developed ICANS. Fifteen patients experienced concurrent CRS and ICANS. However, no significant differences were noted in CR or MRD-negative CR rates between patients with and without CRS/ICANS. Furthermore, no significant difference was noted in leukemia-free survival (LFS) (p = 0.869 for CRS and p = 0.276 for ICANS) or overall survival (OS) (p = 0.677 for CRS and p = 0.326 for ICANS) between patients with and without CRS/ICANS. Similarly, patients with concurrent CRS and ICANS exhibited no differences in OS and LFS when compared with other patients. Multivariate analysis showed that the development of CRS and ICANS was not associated with any difference in OS and LFS.Conclusion Patients with CRS/ICANS experience similar clinical outcomes compared with those without CRS/ICANS following anti-CD19 CAR-T therapy.
引用
收藏
页数:10
相关论文
共 50 条
[31]   CAR-T cells targeting CCR9 and CD1a for the treatment of T cell acute lymphoblastic leukemia [J].
Tirado, Nestor ;
Fidyt, Klaudyna ;
Mansilla, Maria Jose ;
Garcia-Perez, Alba ;
Martinez-Moreno, Alba ;
Vinyoles, Meritxell ;
Alcain, Juan ;
Garcia-Peydro, Marina ;
Roca-Ho, Heleia ;
Fernandez-Fuentes, Narcis ;
Guerrero-Murillo, Mercedes ;
Falgas, Aida ;
Velasco-Hernandez, Talia ;
Bueno, Clara ;
Panelli, Patrizio ;
Mulens-Arias, Vladimir ;
Apostolov, Apostol ;
Engel, Pablo ;
Gonzalez, Europa Azucena ;
Vick, Binje ;
Jeremias, Irmela ;
Caye-Eude, Aurelie ;
Baruchel, Andre ;
Cave, Helene ;
Genesca, Eulalia ;
Ribera, Jordi ;
Diaz-Beya, Marina ;
Martinez-Sanchez, Maria Victoria ;
Fuster, Jose Luis ;
Lopez, Adela Escudero ;
Minguillon, Jordi ;
Perez-Martinez, Antonio ;
Ramirez-Orellana, Manuel ;
Torrebadell, Montserrat ;
Diaz, Victor M. ;
Toribio, Maria L. ;
Sanchez-Martinez, Diego ;
Menendez, Pablo .
JOURNAL OF HEMATOLOGY & ONCOLOGY, 2025, 18 (01)
[32]   A phase I study of CAR-T bridging HSCT in patients with acute CD19+relapse/refractory B-cell leukemia [J].
Ma, Yongyong ;
Zhang, Shenghui ;
Fang, Hongliang ;
Yu, Kang ;
Jiang, Songfu .
ONCOLOGY LETTERS, 2020, 20 (04)
[33]   Efficacy and safety of anti-CD19 CAR-T in a mouse model of IgG4-related disease [J].
Sun, Yeting ;
Huang, Sicheng ;
Zhang, Bo ;
Peng, Yu ;
Lu, Hui ;
Jia, Yimeng ;
Sun, Ruijie ;
Zhang, Fenghua ;
Zhou, Jiaxin ;
Peng, Linyi ;
Li, Mengtao ;
Zhang, Wen ;
Fei, Yunyun .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2025, 145
[34]   Anti-CD19 antibody cotreatment enhances serial killing activity of anti-CD19 CAR-T/-NK cells and reduces trogocytosis [J].
Koh, Seung Kwon ;
Kim, Hyojin ;
Han, Bohwa ;
Jo, Hantae ;
Doh, Junsang ;
Park, Jeehun ;
Ha Nguyen, Minh ;
Kim, Hyun-Young ;
Kim, Haneul ;
Lee, Seung-Hwan ;
Kim, Chan Hyuk ;
Cho, Duck .
BLOOD, 2025, 145 (09) :956-969
[35]   Donor-derived Anti-CD19 CAR T cells GC007g for relapsed or refractory B-cell acute lymphoblastic leukemia after allogeneic HSCT: a phase 1 trial [J].
Luo, Yi ;
Gao, Lei ;
Liu, Jia ;
Yang, Luxin ;
Wang, Lu ;
Lai, Xiaoyu ;
Gao, Shichun ;
Liu, Lizhen ;
Zhao, Lu ;
Ye, Yishan ;
Wang, Manning ;
Shen, Lianjun ;
Cao, W. William ;
Wang, Dongrui ;
Li, Wenling ;
Zhang, Xi ;
Huang, He .
ECLINICALMEDICINE, 2024, 67
[36]   Successful Treatment of Refractory and Relapsed CNS Acute Lymphoblastic Leukemia With CD-19 CAR-T Immunotherapy: A Case Report [J].
Htun, Kyaw Thu ;
Gong, Qiang ;
Ma, Le ;
Wang, Ping ;
Tan, Ya ;
Wu, Guangsheng ;
Chen, Jieping .
FRONTIERS IN ONCOLOGY, 2021, 11
[37]   CAR-T Cell Therapy for Acute Lymphoblastic Leukemia: Transforming the Treatment of Relapsed and Refractory Disease [J].
Katherine C. Pehlivan ;
Brynn B. Duncan ;
Daniel W. Lee .
Current Hematologic Malignancy Reports, 2018, 13 :396-406
[38]   Modified EASIX scores predict severe CRS/ICANS in patients with acute myeloid leukemia following CLL1 CAR-T cell therapy [J].
Zhao, Yifan ;
Zhang, Xiaomei ;
Zhang, Meng ;
Guo, Ruiting ;
Zhang, Yi ;
Pu, Yedi ;
Zhu, Haibo ;
Liu, Pengjiang ;
Zhang, Yu ;
He, Xiaoyuan ;
Lyu, Cuicui ;
Lyu, Hairong ;
Xiao, Xia ;
Zhao, Mingfeng .
ANNALS OF HEMATOLOGY, 2024, 103 (03) :969-980
[39]   Optimizing the Clinical Impact of CAR-T Cell Therapy in B-Cell Acute Lymphoblastic Leukemia: Looking Back While Moving Forward [J].
Safarzadeh Kozani, Pouya ;
Safarzadeh Kozani, Pooria ;
Rahbarizadeh, Fatemeh .
FRONTIERS IN IMMUNOLOGY, 2021, 12
[40]   An owner's manual for CD19 "CAR"-T cell therapy in managing pediatric and young adult B-cell acute lymphoblastic leukemia [J].
Laetsch, Theodore W. ;
Yanik, Gregory A. ;
Boyer, Michael W. ;
Rheingold, Susan R. .
BLOOD REVIEWS, 2021, 50