Addition of the mammalian target of rapamycin inhibitor, everolimus, to consolidation therapy in acute myeloid leukemia: experience from the UK NCRI AML17 trial.
Addition of the mammalian target of rapamycin inhibitor, everolimus, to consolidation therapy in acute myeloid leukemia: experience from the UK NCRI AML17 trial.
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DOI：
10.3324/haematol.2018.189514
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发表时间：
2018-10
期刊：
影响因子：
10.1
通讯作者：
UK NCRI AML Study Group
中科院分区：
文献类型：
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作者：
Burnett AK;Das Gupta E;Knapper S;Khwaja A;Sweeney M;Kjeldsen L;Hawkins T;Betteridge SE;Cahalin P;Clark RE;Hills RK;Russell NH;UK NCRI AML Study Group
作为英国NCRI AML 17试验的一部分，缓解期急性髓性白血病成人患者可以随机接受雷帕霉素抑制剂依维莫司的哺乳动物靶点，并随后进行诱导后化疗。339例患者随机（2：1）接受依维莫司或不接受依维莫司，化疗疗程之间最多84天。主要终点是无复发生存期。5年时无复发生存率无差异[29%对40%;比值比1.19（0.9-1.59）P=0.2]，累积复发率[60% vs 54%：比值比1.12（0.82-1.52）：P=0.5]或总生存期[45% vs 58%：比值比1.3（0.94-1.81）：P=0.11]。由于依维莫司组死亡率过高，没有任何证据表明疾病得到有效控制，独立的数据监测委员会建议在随机化339/600例患者后终止研究。依维莫司的给药剂量是可变的，但没有证据表明给予足够剂量的患者与未给予治疗的患者相比有临床获益。这项研究表明，在化疗中加入哺乳动物雷帕霉素靶点抑制剂没有任何益处。
As part of the UK NCRI AML17 trial, adult patients with acute myeloid leukemia in remission could be randomized to receive the mammalian target of rapamycin inhibitor everolimus, sequentially with post-induction chemotherapy. Three hundred and thirty-nine patients were randomised (2:1) to receive everolimus or not for a maximum of 84 days between chemotherapy courses. The primary endpoint was relapse-free survival. At 5 years there was no difference in relapse-free survival [29% versus 40%; odds ratio 1.19 (0.9-1.59) P=0.2], cumulative incidence of relapse [60% versus 54%: odds ratio 1.12 (0.82-1.52): P=0.5] or overall survival [45% versus 58%: odds ratio 1.3 (0.94-1.81): P=0.11]. The independent Data Monitoring Committee advised study termination after randomization of 339 of the intended 600 patients because of excess mortality in the everolimus arm without any evidence of beneficial disease control. The delivery of the everolimus dose was variable, but there was no evidence of clinical benefit in patients with adequate dose delivery compared with no treatment. This study suggests that the addition of mammalian target of rapamycin inhibition to chemotherapy provides no benefit.