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新型CD19特异性T细胞衔接抗体构建体blinatumomab的临床应用及安全性评估

Clinical applications and safety evaluation of the new CD19 specific T-cell engager antibody construct blinatumomab.

作者信息

Wilke Anne C, Gökbuget Nicola

机构信息

a University Hospital , Department of Medicine II , Frankfurt , Germany.

出版信息

Expert Opin Drug Saf. 2017 Oct;16(10):1191-1202. doi: 10.1080/14740338.2017.1338270. Epub 2017 Aug 20.

Abstract

Blinatumomab is a T-cell engager antibody construct with dual specificity for CD19 and CD3, inducing serial lysis of CD19 positive B cells by redirecting cytotoxic T cells. It has been approved for the indication of Ph chromosome negative relapsed or refractory B-acute lymphoblastic leukemia (ALL), but has also been tested in ALL with minimal residual disease, relapsed Ph/BCR-ABL positive ALL, relapsed ALL in pediatric patients and relapsed or refractory non-Hodgkin's lymphoma (NHL). Adverse events have been mainly related to infection and hematological toxicities, as well as cytokine release syndrome and neurotoxicity. Areas covered: The review will discuss mechanisms of action, published literature on efficacy in ALL and NHL, specific aspects of administration, frequent adverse events and practical management. Expert opinion: Blinatumomab represents an effective new treatment for highly resistant relapsed/refractory B-precursor ALL. Practical handling bears challenges due to application as four week continous infusion and specific adverse effects which can be well handled by experienced centers. Most promising outcomes are reported for patients with resistant disease but lower tumor load such as MRD positive ALL patients. Future studies will focus on the use of blinatumomab during first-line therapy and the role of stem cell transplantation after blinatumomab treatment.

摘要

博纳吐单抗是一种对CD19和CD3具有双重特异性的T细胞衔接抗体构建体,通过重定向细胞毒性T细胞诱导CD19阳性B细胞的连续裂解。它已被批准用于治疗费城染色体阴性复发或难治性B细胞急性淋巴细胞白血病(ALL),但也已在微小残留病的ALL、复发的费城染色体/BCR-ABL阳性ALL、儿科患者复发的ALL以及复发或难治性非霍奇金淋巴瘤(NHL)中进行了测试。不良事件主要与感染和血液学毒性以及细胞因子释放综合征和神经毒性有关。涵盖领域:本综述将讨论其作用机制、关于ALL和NHL疗效的已发表文献、给药的具体方面、常见不良事件及实际管理。专家意见:博纳吐单抗是治疗高度耐药复发/难治性B前体ALL的一种有效新疗法。由于采用四周连续输注以及特定的不良反应,实际操作存在挑战,但经验丰富的中心能够很好地应对。对于耐药但肿瘤负荷较低的患者,如微小残留病阳性ALL患者,报告的疗效最有前景。未来的研究将集中于博纳吐单抗在一线治疗中的应用以及博纳吐单抗治疗后干细胞移植的作用。

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