文章：

急性髓系白血病新兴疗法的新方向：下一篇章

New directions for emerging therapies in acute myeloid leukemia: the next chapter

原文发布日期：2020-10-30

DOI: 10.1038/s41408-020-00376-1

类型: Review Article

开放获取: 是

英文摘要：

Conventional therapy for acute myeloid leukemia is composed of remission induction with cytarabine- and anthracycline-containing regimens, followed by consolidation therapy, including allogeneic stem cell transplantation, to prolong remission. In recent years, there has been a significant shift toward the use of novel and effective, target-directed therapies, including inhibitors of mutant FMS-like tyrosine kinase 3 (FLT3) and isocitrate dehydrogenase (IDH), the B-cell lymphoma 2 inhibitor venetoclax, and the hedgehog pathway inhibitor glasdegib. In older patients the combination of a hypomethylating agent or low-dose cytarabine, venetoclax achieved composite response rates that approximate those seen with standard induction regimens in similar populations, but with potentially less toxicity and early mortality. Preclinical data suggest synergy between venetoclax and FLT3- and IDH-targeted therapies, and doublets of venetoclax with inhibitors targeting these mutations have shown promising clinical activity in early stage trials. Triplet regimens involving the hypomethylating agent and venetoclax with FLT3 or IDH1/2 inhibitor, the TP53-modulating agent APR-246 and magrolimab, myeloid cell leukemia-1 inhibitors, or immune therapies such as CD123 antibody-drug conjugates and programmed cell death protein 1 inhibitors are currently being evaluated. It is hoped that such triplets, when applied in appropriate patient subsets, will further enhance remission rates, and more importantly remission durations and survival.
 

摘要翻译： 

急性髓系白血病的常规治疗包括采用含阿糖胞苷和蒽环类药物的方案进行缓解诱导，随后通过巩固治疗（包括异基因干细胞移植）以延长缓解期。近年来，治疗模式已显著转向使用新型高效的靶向疗法，包括突变型FMS样酪氨酸激酶3（FLT3）抑制剂、异柠檬酸脱氢酶（IDH）抑制剂、B细胞淋巴瘤2抑制剂维奈克拉以及 Hedgehog 信号通路抑制剂格拉斯吉布。在老年患者中，低甲基化药物或低剂量阿糖胞苷联合维奈克拉的方案实现了与标准诱导方案相近的复合缓解率，且潜在毒性和早期死亡率可能更低。临床前数据表明维奈克拉与FLT3、IDH靶向治疗存在协同作用，早期试验中维奈克拉分别与这两种突变抑制剂组成的双药方案已显示出积极临床活性。目前正在评估的三药联合方案包括：低甲基化药物联合维奈克拉与FLT3或IDH1/2抑制剂、TP53调节剂APR-246及马格罗利单抗、髓样细胞白血病1抑制剂，以及CD123抗体-药物偶联物与程序性细胞死亡蛋白1抑制剂等免疫疗法。这些三药方案在适宜患者群体中的应用，有望进一步提升缓解率，更重要的是延长缓解持续时间与生存期。

原文链接：

New directions for emerging therapies in acute myeloid leukemia: the next chapter