Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia.
Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia.
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DOI：
10.1056/nejmoa1609783
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发表时间：
2017-03-02
期刊：
影响因子：
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通讯作者：
Topp MS
中科院分区：
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作者：
Kantarjian H;Stein A;Gökbuget N;Fielding AK;Schuh AC;Ribera JM;Wei A;Dombret H;Foà R;Bassan R;Arslan Ö;Sanz MA;Bergeron J;Demirkan F;Lech-Maranda E;Rambaldi A;Thomas X;Horst HA;Brüggemann M;Klapper W;Wood BL;Fleishman A;Nagorsen D;Holland C;Zimmerman Z;Topp MS
Blinatumomab是一种双特异性单克隆抗体，可使cd3阳性T细胞识别和消除cd19阳性急性淋巴细胞白血病（ALL）原细胞。基于单组试验，Blinatumomab已被批准用于复发或难治性b细胞前体ALL患者，该试验显示出疗效和可控的毒性作用。在这个多机构的3期临床试验中，我们随机分配重度预处理b细胞前体ALL的成人患者，以2:1的比例接受blinatumomab或标准治疗化疗。主要终点为总生存期。405名患者被随机分配接受blinatumomab（271名患者）或化疗（134名患者），376名患者接受了至少一次剂量。布利纳单抗组的总生存期明显长于化疗组。布利纳单抗组的中位总生存期为7.7个月，化疗组的中位总生存期为4.0个月（布利纳单抗与化疗的死亡风险比为0.71；95%可信区间[CI]， 0.55 ~ 0.93; P = 0.01）。治疗开始后12周内，blinatumumab组的缓解率显著高于化疗组，无论是完全缓解和完全血液学恢复（34% vs. 16%， P<0.001），还是完全缓解和完全、部分或不完全血液学恢复（44% vs. 25%， P<0.001）。与化疗相比，blinatumomab治疗导致更高的无事件生存率（6个月估计，31%对12%；在完全缓解（完全、部分或不完全血液学恢复或死亡）后复发事件的风险比，0.55;95% CI， 0.43至0.71；P<0.001），以及更长的中位缓解持续时间（7.3个月对4.6个月）。每个治疗组共有24%的患者接受了同种异体干细胞移植。blinatumumab组87%的患者报告了3级或以上不良事件，化疗组92%的患者报告了3级或以上不良事件。在复发或难治性b细胞前体ALL的成年患者中，blinatumomab治疗的总生存期明显长于化疗。（由Amgen资助；TOWER ClinicalTrials.gov编号：NCT02013167）
Blinatumomab, a bispecific monoclonal antibody construct that enables CD3-positive T cells to recognize and eliminate CD19-positive acute lymphoblastic leukemia (ALL) blasts, was approved for use in patients with relapsed or refractory B-cell precursor ALL on the basis of single-group trials that showed efficacy and manageable toxic effects. In this multi-institutional phase 3 trial, we randomly assigned adults with heavily pretreated B-cell precursor ALL, in a 2:1 ratio, to receive either blinatumomab or standard-of-care chemotherapy. The primary end point was overall survival. Of the 405 patients who were randomly assigned to receive blinatumomab (271 patients) or chemotherapy (134 patients), 376 patients received at least one dose. Overall survival was significantly longer in the blinatumomab group than in the chemotherapy group. The median overall survival was 7.7 months in the blinatumomab group and 4.0 months in the chemotherapy group (hazard ratio for death with blinatumomab vs. chemotherapy, 0.71; 95% confidence interval [CI], 0.55 to 0.93; P = 0.01). Remission rates within 12 weeks after treatment initiation were significantly higher in the blinatumomab group than in the chemotherapy group, both with respect to complete remission with full hematologic recovery (34% vs. 16%, P<0.001) and with respect to complete remission with full, partial, or incomplete hematologic recovery (44% vs. 25%, P<0.001). Treatment with blinatumomab resulted in a higher rate of event-free survival than that with chemotherapy (6-month estimates, 31% vs. 12%; hazard ratio for an event of relapse after achieving a complete remission with full, partial, or incomplete hematologic recovery, or death, 0.55; 95% CI, 0.43 to 0.71; P<0.001), as well as a longer median duration of remission (7.3 vs. 4.6 months). A total of 24% of the patients in each treatment group underwent allogeneic stem-cell transplantation. Adverse events of grade 3 or higher were reported in 87% of the patients in the blinatumomab group and in 92% of the patients in the chemotherapy group. Treatment with blinatumomab resulted in significantly longer overall survival than chemotherapy among adult patients with relapsed or refractory B-cell precursor ALL. (Funded by Amgen; TOWER ClinicalTrials.gov number, NCT02013167.)