New directions for emerging therapies in acute myeloid leukemia: the next chapter.
New directions for emerging therapies in acute myeloid leukemia: the next chapter.
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DOI：
10.1038/s41408-020-00376-1
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发表时间：
2020-10-30
影响因子：
12.8
通讯作者：
DiNardo CD
中科院分区：
文献类型：
--
作者：
Daver N;Wei AH;Pollyea DA;Fathi AT;Vyas P;DiNardo CD
急性髓性白血病的常规治疗包括用含阿糖胞苷和蒽环类药物的方案诱导缓解，随后进行巩固治疗，包括异基因干细胞移植，以延长缓解。近年来，已经出现了向使用新型和有效的靶向治疗的重大转变，包括突变FMS样酪氨酸激酶3（FLT 3）和异柠檬酸脱氢酶（IDH）的抑制剂，B细胞淋巴瘤2抑制剂venetoclax和hedgehog途径抑制剂glasdegib。在老年患者中，低甲基化药物或低剂量阿糖胞苷、维奈托克联合治疗的复合缓解率与类似人群中标准诱导方案的复合缓解率接近，但毒性和早期死亡率可能更低。临床前数据表明，维奈托克与FLT 3和IDH靶向治疗之间存在协同作用，维奈托克与靶向这些突变的抑制剂的双重组合在早期试验中显示出有希望的临床活性。目前正在评估三联方案，包括低甲基化剂和维奈托克与FLT 3或IDH 1/2抑制剂、TP 53调节剂APR-246和magrolimab、髓系细胞白血病-1抑制剂或免疫疗法（如CD 123抗体-药物偶联物和程序性细胞死亡蛋白1抑制剂）。希望这样的三联体，当应用于适当的患者亚组时，将进一步提高缓解率，更重要的是缓解持续时间和生存率。
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.
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DOI：
10.1016/s1470-2045(18)30240-7
发表时间：
2018-07
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Cortes J;Perl AE;Döhner H;Kantarjian H;Martinelli G;Kovacsovics T;Rousselot P;Steffen B;Dombret H;Estey E;Strickland S;Altman JK;Baldus CD;Burnett A;Krämer A;Russell N;Shah NP;Smith CC;Wang ES;Ifrah N;Gammon G;Trone D;Lazzaretto D;Levis M
通讯作者：
Levis M
影响因子：
4
作者：
Chen EC;Fathi AT;Brunner AM
通讯作者：
Brunner AM
影响因子：
158.5
作者：
DiNardo, C. D.;Stein, E. M.;Kantarjian, H. M.
通讯作者：
Kantarjian, H. M.
影响因子：
45.3
作者：
Burnett, Alan K.;Hills, Robert K.;Wheatley, Keith
通讯作者：
Wheatley, Keith
影响因子：
--
作者：
Bogenberger J;Whatcott C;Hansen N;Delman D;Shi CX;Kim W;Haws H;Soh K;Lee YS;Peterson P;Siddiqui-Jain A;Weitman S;Stewart K;Bearss D;Mesa R;Warner S;Tibes R
通讯作者：
Tibes R