Song F M, Hu Y X, Zhang M M, Wu W W, Xu H J, Zhang H S, Huang H, Wei G Q
Bone Marrow Transplantation Center, Institute of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou 311100, China.
Clinical Transformation Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200438, China.
Zhonghua Xue Ye Xue Za Zhi. 2022 Aug 14;43(8):651-656. doi: 10.3760/cma.j.issn.0253-2727.2022.08.006.
This study aimed to evaluate the safety and efficacy of humanized CD19-targeted chimeric antigen receptor T-cell (CAR-T) in patients with relapsed/refractory acute B cell lymphoblastic leukemia (R/R B-ALL) . The clinical data of 41 patients with R/R B-ALL treated with humanized CD19-targeted CAR-T cells in the First Affiliated Hospital of Zhejiang University School of Medicine from February 2020 to July 2021 were analyzed. Cytokine release syndrome occurred in all patients, and 63.4% (26/41) were grades 1-2. Immune effector cell-associated neurotoxicity syndrome developed in three patients. On median day 15 (9-47) , the complete remission rate was 95.1% (39/41) , of which 38 patients tested negative for bone marrow minimal residual disease detected by flow cytometry. Among the 39 patients with complete remission, 17 patients did not receive further treatment, and 70.6% (12/17) remained in remission at the end of follow-up, with a progression-free survival of 11.6 months of the two patients with the earliest infusion. Another 17 patients underwent consolidation allogeneic hematopoietic stem cell transplantation (10 cases) or CD22 CAR-T cell sequential therapy (seven cases) after remission, and 76.5% (13/17) of the patients were still in remission at the end of follow-up. The remaining five patients who did not receive consolidation therapy relapsed at a median of 72 (55-115) days after CAR-T cell therapy. In patients with R/R B-ALL, the humanized CD19-targeted CAR-T cells had a high response and manageable toxicity.
本研究旨在评估人源化抗CD19嵌合抗原受体T细胞（CAR-T）治疗复发/难治性急性B淋巴细胞白血病（R/R B-ALL）患者的安全性和疗效。分析了2020年2月至2021年7月在浙江大学医学院附属第一医院接受人源化抗CD19 CAR-T细胞治疗的41例R/R B-ALL患者的临床资料。所有患者均发生细胞因子释放综合征，63.4%（26/41）为1-2级。3例患者发生免疫效应细胞相关神经毒性综合征。在第15天（9-47天）的中位时间，完全缓解率为95.1%（39/41），其中38例患者通过流式细胞术检测骨髓微小残留病呈阴性。在39例完全缓解的患者中，17例未接受进一步治疗，70.6%（12/17）在随访结束时仍处于缓解状态，最早输注的2例患者无进展生存期为11.6个月。另外17例患者在缓解后接受了巩固性异基因造血干细胞移植（10例）或CD22 CAR-T细胞序贯治疗（7例），76.5%（13/17）的患者在随访结束时仍处于缓解状态。其余5例未接受巩固治疗的患者在CAR-T细胞治疗后中位72（55-115）天复发。在R/R B-ALL患者中，人源化抗CD19 CAR-T细胞具有高反应性且毒性可控。
