FDA Approval: Blinatumomab for Patients with B-cell Precursor Acute Lymphoblastic Leukemia in Morphologic Remission with Minimal Residual Disease
FDA Approval: Blinatumomab for Patients with B-cell Precursor Acute Lymphoblastic Leukemia in Morphologic Remission with Minimal Residual Disease
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DOI：
10.1158/1078-0432.ccr-18-2337
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发表时间：
2019-01-15
影响因子：
11.5
通讯作者：
Pazdur, Richard
中科院分区：
文献类型：
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作者：
Jen, Emily Y.;Xu, Qing;Pazdur, Richard
2018年3月29日，FDA批准Blinatumomab（Blincyto; Amgen，Inc.）用于治疗B细胞前体急性淋巴细胞白血病（BCP ALL）的成人和儿童，首次或第二次完全缓解，微小残留病（MRD）≥ 0.1%。Blinatumomab是一种CD 3xCD 19双特异性抗体，之前获批用于治疗复发性或难治性BCP ALL。加速批准的基础是一项单组试验。对于MRD >= 0.1%的86例首次和第二次完全缓解患者，Blinatumomab治疗1个周期后MRD < 0.01%的转化率分别为85.2% [95%置信区间（CI）：73.8%，93.0%]和72.0%（95%CI：50.6%，87.9%），估计的中位血液学无复发生存期（RFS）为35.2个月（95% CI：0.4-53.5）和12.3个月（95% CI：0.7-42.3）。血液学RFS被认为与患者随后是否接受异基因干细胞移植无关。在既往研究中确立了Blinatumomab的安全性特征，在新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要求在随机试验中确认临床益处。
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.