Harnessing the benefits of available targeted therapies in acute myeloid leukaemia.
Harnessing the benefits of available targeted therapies in acute myeloid leukaemia.
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DOI：
10.1016/s2352-3026(21)00270-2
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Tallman M
中科院分区：
文献类型：
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作者：
Kantarjian H;Short NJ;DiNardo C;Stein EM;Daver N;Perl AE;Wang ES;Wei A;Tallman M
自2017年以来，对急性髓细胞白血病(AML)的研究已使FDA监管部门批准了9种用于AML适应症的药物：bcl2抑制剂ventoclax；两种Flt3抑制剂米哚妥林和吉特利替尼；两种IDH抑制剂ivosidenib(IDH1抑制剂)和enasidenib(IDH2抑制剂)；getuzumab ozogamicin(CD33抗体-药物结合物)；口服、吸收不良的低甲基化制剂(HMA)azacitidine；CPX351(阿糖胞苷和柔红霉素5：1的脂质体制剂)；以及hedgehog抑制剂glasdegib。100%可吸收的HMA地西他滨口服制剂被批准用于MDS和CMML的治疗，并可作为非肠道HMAS的替代品。其中几项批准是作为单一药物疗法或针对狭窄适应症的特定组合，因此提供的治疗价值较差。在这篇综述中，我们讨论了正在进行的研究，这些商业上可用的针对AML的靶向疗法已经在联合使用，并显示出良好的结果。
Acute myeloid leukemia (AML) research has resulted in FDA regulatory approval of nine agents for AML indications since 2017: the BCL2 inhibitor venetoclax; two FLT3 inhibitors, midostaurin and gilteritinib; two IDH inhibitors, ivosidenib (IDH1 inhibitor) and enasidenib (IDH2 inhibitor); gemtuzumab ozogamicin (CD33 antibody-drug conjugate); the oral, poorly absorbable hypomethylating agent (HMA) azacitidine; CPX351 (liposomal formulation of 5:1 ratio of cytarabine and daunorubicin); and the hedgehog inhibitor glasdegib. A 100% absorbable oral formulation of the HMA decitabine was approved for the therapy of MDS and CMML and may be used as an alternative to parenteral HMAs. Several of the approvals are as single-agent therapies or in specific combinations for narrow indications, thus offering a poor treatment value. In this review, we discuss ongoing research with these commercially available targeted therapies for AML being used already in combinations that are demonstrating favorable results.