人源化抗CD19嵌合抗原受体T细胞治疗急性B淋巴细胞白血病的临床研究

Clinical Efficacy of Humanized Anti-CD19 Chimeric Antigen Receptor T Cells in the Treatment of Acute B Lymphocytic Leukemia

目的:研究人源化CD19 CAR-T细胞治疗难治/复发性B-ALL患者的安全性和有效性。方法:入组的患者为15例既往未接受鼠源CD19 CAR-T细胞治疗的复发/难治的B-ALL儿童和成人患者。患者在氟达拉滨和环磷酰胺为基础的预处理化疗后,接受了1×10^6/kg的自体人源化CD19 CAR-T(Hcart19)细胞的输注。在患者回输CAR-T细胞后观察其治疗的安全性及有效性。结果:15名患者中,13/14(92.9%)可评价的患者在Hcart19输注后30 d获得了完全缓解(CR)或者CR伴血细胞不完全恢复(Cri)。180 d时总生存率及无病生存率分别达到73.3%和69.2%。累积复发率及非复发死亡率分别是24.5%和7.7%。15例患者中有12名患者(80%)发生了1-2级的细胞因子释放综合征(CRS),3名患者(20.0%)发生了3-5级的CRS,而只有1名患者(6.7%)发生了可逆性神经毒性。结论:hCART19s可有效治疗复发/难治的成人及儿童B-ALL患者,且治疗相关的CRS及神经毒性发生率较低。

Objective:To study the safety and effectiveness of humanized CD19-targeted CAR-T cells(hCART19s)for treatment of patients with refractory/relapsed(R/R)B-ALL.Methods:The analyzed patients were 15 children and adults with relapsed/refractory B-ALL who not received treatment with murine CD19 CAR-T cells.The patients received a single dose(1×10^6/kg)of autologous hCART19 infusion after lymphodepletion chemotherapy based on cyclophosphamide and fludarabine.Results:Among the 15 patients,13/14(92.9%)evaluable patients achieved complete remission(CR)or CR with incomplete recovery of blood cells(CRi)on day 30 after hCART19s infusion.At day 180 after the infusion,the overall survival rate was 73.3%,and the leukemia-free survival rate was 69.2%.The cumulative incidence of relapse was 24.5%and non-relapse mortality rate was 7.7%.During treatment,12/15 patients(80%)developed cytokine release syndrome(CRS)of grade 1-2,and 3 patients(20.0%)developed CRS of grade 3-5.Only one patient(6.7%)suffered from the reversible neurotoxicity.Conclusion:hCART19 s can effectively treat refractory/relapsed(R/R)adult and children with B-ALL,and the incidence of treatment-related CRS and neurotoxicity is low.