博纳吐单抗治疗成人复发/难治Ph阴性急性B淋巴细胞白血病临床研究  

Clinical Study of Blinatumomab in the Treatment of Adult Relapsed/Refractory Ph-Negative Acute B-Lymphoblastic Leukemia

作　　者：欧阳敏 张亚运 史琳 刘建新 王春键 王芳[1] 张瑶 李燕 张梅香[1] 胡文青 任汉云 江滨 OUYANG Min;ZHANG Ya-Yun;SHI Lin;LIU Jian-Xin;WANG Chun-Jian;WANG Fang;ZHANG Yao;LI Yan;ZHANG Mei-Xiang;HU Wen-Qing;REN Han-Yun;JIANG Bin(Department of Hematology,Peking University Intenational Hospital,Beijing 102206,China)

机构地区：[1]北京大学国际医院血液科,北京102206

出　　处：《中国实验血液学杂志》2023年第5期1352-1357,共6页Journal of Experimental Hematology

摘　　要：目的:探讨CD19/CD3双抗体博纳吐单抗(blinatumomab)治疗成人难治和复发性Ph阴性急性B淋巴细胞白血病(RR-B-ALL)的疗效及安全性。方法:共10例成人R/R B-ALL患者接受博纳吐单抗治疗,每治疗周期用药28 d,停14 d。第1个周期的d 1-7 d剂量为9μg/d,如无不良反应,d 8-28剂量为28μg/d。从第2个周期开始,每日剂量均为28μg。观察治疗后白血病缓解情况、生存期(EFS和OS)及不良反应。结果:可评价疗效患者9例,4例在1个疗程后获得CR,1例在2个疗程后获CR,总缓解率为55.6%(5/9例),中位EFS为4(1-12)个月,中位OS为6(2-44)个月。10例患者中9例出现不同程度的发热;血清IL-6、IL-10、IL-17和IFN-γ等细胞因子水平发现不同程度升高;2例患者分别因神经毒性和CRS中断治疗1周后恢复用药;1例患者因3级CRS停药并死于热带念珠菌血症。结论:博纳吐单抗用于治疗复发/难治性B-ALL患者获得较好的缓解率,但缓解期维持时间较短。药物相关不良反应主要为CRS和神经毒性,细胞因子IL-6、IL-10、IL-17和IFN-γ可以作为监测CRS的指标。该双特异性单克隆抗体为R/R-ALL患者异基因造血干细胞移植提供了机会。Objective:To investigate the efficacy and safety of CD19/CD3 bisecific monoclonalantibody(Blinatumomab)in the treatment of adult patients with relapsed/refractory Ph-negative acute B-lymphoblastic leukemia(R/R-B-ALL).Methods:Ten adult R/R B-ALL patients were all treated with Blinatumomab.Each treatment cycle was administered for 28 days and stopped for 14 days.The dose was 9μg/day for the first 7 days of cycle 1,and 28μg/day for days 8-28 if there were no adverse reactions.From the second cycle onwards,the daily dose was 28μg.The remission,survival time(EFS and OS)and adverse reactions were observed after treatment.Results:Nine patients with curative effect could be evaluated.Four patients achieved CR after one course,and one patient achieved CR after two courses,the overall remission rate was 55.6%(5/9).The median EFS was 4 months(1-12 months),and the median OS was 6 months(2-44 months).Nine of the 10 patients had fever of different degrees.Serum levels of cytokines such as IL-6,IL-10,IL-17 and IFN-γincreased.Two patients resumed medication after 1 week of treatment interruption due to neurotoxicity and CRS,respectively.One patient was discontinued due to grade 3 CRS and died of tropical candidiaemia.Conclusion:Blinatumomab has a good response rate in the treatment of relapsed/refractory B-ALL patients,but the duration of remission is shorter.Drug-related adverse reactions are mainly CRS and neurotoxicity.Inflammatory factors IL-6,IL-10,IL-17 and IFN-γcan be used as indicators to monitor CRS.The bisspecificity MAbs provide an opportunity for subsequent allogeneic hematopoietic stem cell transplantation in R/R-B-ALL patients.

关 键 词：博纳吐单抗 急性B淋巴细胞白血病 复发/难治 细胞因子释放综合症 

分 类 号：R733.71[医药卫生—肿瘤]