Abstract:
Background: B-cell leukemia/lymphoma-2 (BCL-2) protein is an important part of apoptotic pathway, which is overexpressed in chronic lymphocytic leukemia cells, non-Hodgkin lymphoma cells, and myeloma cells. Venetoclax (ABT-199/GDC-0199) is a highly selective bioavailable inhibitor of BCL-2 protein, which is more effective and less valid against BCL-xL in BCL2-dependent leukemia and lymphoma cell. Method: We searched PubMed database using retrieval keyword venetoclax, ABT-199, or GDC-0199 and investigated the data of the involved articles. Considering variability in different studies, the overall response rate was collected to assess the efficacy. Meanwhile, adverse events (AEs) were summarized, and event rates were calculated to assess the safety. Results: When patients were treated with venetoclax monotherapy, the most common AEs were nausea, diarrhea, neutropenia, fatigue and thrombocytopenia, and neutropenia. In addition, thrombocytopenia, anemia, febrile neutropenia, and leukopenia appeared more common and are considered as the severe AEs (defined as grade ≥ 3 AEs). Although the occurrence of thrombocytopenia was relatively high, it was not the most severe type. When compared with patients treated with venetoclax and other drugs, nausea, diarrhea, and thrombocytopenia were still the most common AEs occurrence in the patients of all the grade. The overall event rate was 73%, which is quite satisfactory. Conclusion: Venetoclax is a mild and efficient drug in treating advanced hematological malignancy, which can be specially fit for the chronic lymphocytic leukemia patients with del[17p], and AEs are well tolerable. Few tumor lysis syndrome occurred after taking the drugs. The AEs aroused by venetoclax, and the combination is well tolerable. Therefore, the use of venetoclax monotherapy or its combination with other therapies is desirable in hematological malignancy.
摘要:
背景:B细胞白血病/淋巴瘤-2(BCL-2)蛋白是细胞凋亡通路的重要组成部分,在慢性淋巴细胞白血病细胞中过度表达,非霍奇金淋巴瘤细胞,和骨髓瘤细胞。维奈托克(ABT-199/GDC-0199)是一种高度选择性的BCL-2蛋白生物利用抑制剂,在BCL2依赖性白血病和淋巴瘤细胞中对BCL-xL更有效,对BCL-xL无效。方法:我们使用检索关键字venetoclax搜索PubMed数据库,ABT-199或GDC-0199,并调查了相关文章的数据。考虑到不同研究的可变性,收集总有效率以评估疗效.同时,总结了不良事件(AE),并计算事件发生率以评估安全性.结果:当患者接受维奈托克单药治疗时,最常见的不良事件是恶心,腹泻,中性粒细胞减少症,疲劳和血小板减少症,和中性粒细胞减少症.此外,血小板减少症,贫血,发热性中性粒细胞减少症,白细胞减少症更常见,被认为是严重的AE(定义为≥3级AE)。尽管血小板减少的发生率相对较高,这不是最严重的类型。与接受维奈托克和其他药物治疗的患者相比,恶心,腹泻,和血小板减少仍然是所有级别患者中最常见的AE发生。总体事件发生率为73%,这是相当令人满意的。结论:维奈托克是治疗晚期血液系统恶性肿瘤的一种温和、有效的药物。特别适合于患有del[17p]的慢性淋巴细胞白血病患者,和AE是可以容忍的。服用药物后很少发生肿瘤溶解综合征。威尼托克引起的不良事件,这种组合是可以容忍的。因此,在血液系统恶性肿瘤中,需要使用维奈托克单一疗法或其与其他疗法的组合。