Clinical and pharmacologic aspects of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia.
Clinical and pharmacologic aspects of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia.
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DOI：
10.2147/cpaa.s42689
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Advani AS
中科院分区：
文献类型：
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作者：
Portell CA;Wenzell CM;Advani AS
成人急性淋巴细胞白血病（ALL）仍然是一种具有挑战性的疾病，需要新的治疗方法。前体B ALL占80%的病例，几乎所有前体B ALL患者都表达CD19抗原。双特异性T细胞接合抗体是新型生物工程蛋白。双特异性T细胞结合抗体Blinatumomab将多克隆T细胞与表达CD 19的B细胞结合。通过与CD 3和CD 19结合，Blinatumomab可使这些T细胞与恶性B细胞紧密接触，并增强T细胞诱导的细胞毒性细胞杀伤。Blinatumomab需要持续静脉输注，因为其半衰期较短，需要持续暴露才能发挥足够的疗效，并降低毒性。一项针对持续或复发性微小残留病的B细胞ALL患者的II期试验显示，完全分子缓解率为80%。细胞因子释放综合征和中枢神经系统事件（如癫痫发作和脑病）是可逆性毒性。在B细胞ALL伴微小残留病中的有希望的结果导致了对这种药物在新诊断和复发的B细胞ALL中的进一步评估。
Acute lymphoblastic leukemia (ALL) in adults remains a challenging disease to treat, and novel therapies are needed. Precursor-B ALL comprises 80% of cases, and the CD19 antigen is expressed in nearly all precursor-B ALL patients. Bispecific T-cell-engaging antibodies are novel bioengineered proteins. The bispecific T-cell-engaging antibody blinatumomab engages polyclonal T cells to CD19-expressing B cells. By binding to both CD3 and CD19, blinatumomab physically brings these T cells in close proximity to malignant B cells and potentiates T-cell-induced cytotoxic cell kill. Blinatumomab requires continuous intravenous infusion due to its short half-life, the need for continuous exposure for the drug to exert sufficient efficacy, and lessened toxicity. A phase II trial of B-cell ALL patients with persistent or relapsed minimal residual disease demonstrated an 80% rate of complete molecular remission. Cytokine-release syndrome and central nervous system events, such as seizures and encephalopathy, are reversible toxicities. Promising results in B-cell ALL with minimal residual disease have led to further evaluation of this drug in newly diagnosed and relapsed B-cell ALL.