Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, Maryland.
Clin Cancer Res. 2019 Jan 15;25(2):473-477. doi: 10.1158/1078-0432.CCR-18-2337. Epub 2018 Sep 25.
On March 29, 2018, the FDA granted accelerated approval for blinatumomab (Blincyto; Amgen, Inc.) for the treatment of adults and children with B-cell precursor acute lymphoblastic leukemia (BCP ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%. Blinatumomab is a CD3xCD19 bispecific antibody approved previously for the treatment of relapsed or refractory BCP ALL. The basis for this accelerated approval was a single-arm trial. For the 86 patients in first and second complete remission with MRD ≥ 0.1%, conversion to MRD < 0.01% was achieved after one cycle of blinatumomab by 85.2% [95% confidence interval (CI): 73.8%, 93.0%] and 72.0% (95% CI: 50.6%, 87.9%), respectively, and the estimated median hematologic relapse-free survivals (RFS) were 35.2 months (95% CI: 0.4-53.5) and 12.3 months (95% CI: 0.7-42.3), respectively. Hematologic RFS was considered substantial independent of whether patients underwent subsequent allogeneic stem cell transplantation. The safety profile for blinatumomab was established in prior studies, and no new safety signals were observed in the new population. Cytokine release syndrome and neurotoxicity remain significant risks. The FDA is requiring confirmation of clinical benefit in a randomized trial.
2018 年 3 月 29 日，美国食品药品监督管理局（FDA）批准blinatumomab（blinatumomab；安进公司）用于治疗处于首次或第二次完全缓解（CR）期、伴有微小残留病灶（MRD）≥0.1%的成人和儿童 B 细胞前体急性淋巴细胞白血病（BCP-ALL）。blinatumomab 是一种 CD3xCD19 双特异性抗体，此前已被批准用于治疗复发或难治性 BCP-ALL。此次加速批准的依据是一项单臂试验。在 86 例处于首次和第二次 CR 期、MRD≥0.1%的患者中，blinatumomab 治疗一个周期后，分别有 85.2%（95%置信区间：73.8%，93.0%）和 72.0%（95%置信区间：50.6%，87.9%）的患者 MRD 转为<0.01%，估计的中位血液学无复发生存（RFS）分别为 35.2 个月（95%置信区间：0.4-53.5）和 12.3 个月（95%置信区间：0.7-42.3）。血液学 RFS 被认为是实质性的，与患者是否接受后续异基因造血干细胞移植无关。blinatumomab 的安全性特征在先前的研究中已确立，在新的人群中未观察到新的安全性信号。细胞因子释放综合征和神经毒性仍然是重大风险。FDA 要求在一项随机试验中确认临床获益。
