Département de Pharmacologie Médicale, CHU de Toulouse, Université Toulouse III - Paul Sabatier, Toulouse, France.
Département d'Hématologie et de Médecine Interne, Institut Universitaire du Cancer-Oncopole, CHU de Toulouse, Toulouse, France.
J Clin Pharm Ther. 2022 Sep;47(9):1337-1351. doi: 10.1111/jcpt.13741. Epub 2022 Jul 29.
Bispecific drugs (BDs) belong to the family of immunotherapies along with checkpoint inhibitors and CAR-T cells. In the field of oncology, BDs are designed to simultaneously bind a tumour antigen on the one side and an antigen present on the surface of effector cells on the other. This review summarizes the information available to date on the first marketed BiTE-format bispecific antibody, blinatumomab BLINCYTO® in acute lymphoblastic leukaemia.
A literature search was conducted in the PubMed database by including studies published in English using the term blinatumomab. Furthermore, bibliographies of selected references were also evaluated for relevant articles. Clinical trial (CT) data were retrieved from clinicaltrials.gov (ongoing trials, adverse events [AEs]) and global pharmacovigilance data were retrieved from VigiBase®.
Blinatumomab is a fusion protein which consists of two single-chain variable fragments arranged in tandem: the first binds the CD19 surface antigen of all B cells and the second targets the CD3 antigen of T cells. Binding of blinatumomab to B and T cells induces apoptosis of B cells after secretion of granzymes and perforins by T cells. T-cell activation results in secretion of pro-inflammatory cytokines and upregulation of activation markers and adhesion molecules on the surface of T cells. The major CTs that led to an indication show increased overall survival with blinatumomab with better efficacy in patients in haematological remission with minimal residual disease ≥10 . The major AEs are cytokine release syndrome, neurotoxicity and hypogammaglobulinemia. The three most frequent system organ classes in CTs are haematological, gastrointestinal and general disorders. These results are also found in VigiBase® but neurological disorders and infections appear more frequently in real life.
This review summarizes the current knowledge of blinatumomab in the literature. The subject of many CTs is to improve the route of administration and expand the indications for treatment.
双特异性药物（BDs）属于免疫疗法家族，与检查点抑制剂和 CAR-T 细胞一起。在肿瘤学领域，BDs 的设计目的是同时结合肿瘤抗原的一侧和效应细胞表面存在的抗原的另一侧。本综述总结了迄今为止关于首批上市的 BiTE 格式双特异性抗体blinatumomab BLINCYTO®在急性淋巴细胞白血病中的信息。
通过在 PubMed 数据库中使用blinatumomab 一词搜索发表的英文研究，进行了文献检索。此外，还评估了选定参考文献的参考文献以获取相关文章。从 clinicaltrials.gov（正在进行的试验、不良事件[AE]）检索临床试验数据，并从 VigiBase®检索全球药物警戒数据。
blinatumomab 是一种融合蛋白，由两个串联排列的单链可变片段组成：第一个结合所有 B 细胞的 CD19 表面抗原，第二个靶向 T 细胞的 CD3 抗原。blinatumomab 与 B 和 T 细胞结合后，T 细胞分泌颗粒酶和穿孔素后诱导 B 细胞凋亡。T 细胞激活导致促炎细胞因子的分泌以及 T 细胞表面激活标志物和粘附分子的上调。导致适应症的主要 CT 显示 blinatumomab 总体生存率增加，在有最小残留疾病≥10 的血液学缓解患者中疗效更好。主要不良事件是细胞因子释放综合征、神经毒性和低丙种球蛋白血症。在 CT 中最常见的三个系统器官类别是血液学、胃肠道和一般疾病。这些结果也在 VigiBase®中发现，但在现实生活中，神经系统疾病和感染更为常见。
本综述总结了文献中关于 blinatumomab 的现有知识。许多 CT 的主题是改善给药途径并扩大治疗适应症。
