Cerrano Marco, Itzykson Raphael
Department of Hematology, Hopital Saint-Louis, Assistance Publique Hopitaux de Paris, Paris Diderot University, Paris, France.
Department of Hematology, Università degli studi di Torino, Turin, Italy.
Curr Oncol Rep. 2019 Feb 4;21(2):16. doi: 10.1007/s11912-019-0764-8.
The extensive genomic characterization of acute myeloid leukemia (AML) led to the identification of a vast number of potential therapeutic targets. We review relevant data that have led to recent approval of new targeted therapies in AML and discuss the most promising drugs currently in development in this disease.
New formulations of cytotoxic agents, namely CPX-351 and gemtuzumab ozogamicin, improve the outcome of defined subgroup of patients. Midostaurin added to intensive chemotherapy is approved in FLT3-mutated AML. More selective FLT3 inhibitors and the IDH inhibitors enasidenib and ivosidenib have shown significant single agent activity in the relapsed setting, and preliminary results of combination strategies are encouraging. The addition of the BCL2 inhibitor venetoclax appears to markedly improve the results of hypomethylating agents. The therapeutic armamentarium of AML now includes novel cytotoxic drugs, drugs targeting recurrent oncogenes, or functional vulnerabilities of leukemic cells. Further work is required to optimize their integration to the current framework of AML management, including allogeneic stem cell transplantation.
急性髓系白血病（AML）广泛的基因组特征鉴定出了大量潜在治疗靶点。我们回顾了促使AML新靶向疗法近期获批的相关数据，并讨论了目前该疾病中最有前景的正在研发的药物。
细胞毒性药物的新制剂，即CPX-351和吉妥珠单抗奥唑米星，改善了特定亚组患者的预后。在强化化疗中加入米哚妥林已被批准用于治疗FLT3突变的AML。更具选择性的FLT3抑制剂以及异柠檬酸脱氢酶（IDH）抑制剂恩西地平与艾伏尼布在复发情况下已显示出显著的单药活性，联合治疗策略的初步结果令人鼓舞。加入BCL2抑制剂维奈克拉似乎能显著改善低甲基化药物的治疗效果。AML的治疗手段现在包括新型细胞毒性药物、靶向复发性致癌基因或白血病细胞功能弱点的药物。需要进一步开展工作以优化将这些药物纳入当前AML管理框架（包括异基因干细胞移植）的方式。
