Randomized Phase II Study of Clofarabine-Based Consolidation for Younger Adults With Acute Myeloid Leukemia in First Remission
Randomized Phase II Study of Clofarabine-Based Consolidation for Younger Adults With Acute Myeloid Leukemia in First Remission
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DOI：
10.1200/jco.2016.70.4551
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发表时间：
2017-04-10
影响因子：
45.3
通讯作者：
Dombret, Herve
中科院分区：
文献类型：
--
作者：
Thomas, Xavier;de Botton, Stephane;Dombret, Herve
目的评价以氯法拉滨为基础的联合化疗(Clara)与常规大剂量阿糖胞苷(HDAC)方案治疗年轻急性髓系白血病(AML)缓解期后化疗的疗效和安全性。221名患者被随机分配接受三个克拉拉或三个HDAC巩固周期。主要终点为无复发生存期(RFS)。结果2年后，CRLA组和HDAC组的RFS分别为58.5%(95%CI，49%至67%)和46.5%(95%CI，37%至55%)。总体而言，110名患者(每组55例)在首次缓解时接受了SCT。在多变量COX调整处理3 SCT交互作用的基础上，在接受SCT前或不接受SCT时，使用HDAC的Clara的HR为0.65(95%CI，0.43至0.98；P=.041)。在敏感性分析中，当首次缓解时接受SCT的患者在SCT时间被审查时，Clara组和HDAC组的2年RFS分别为53.3%(95%CI，39%至66%)和31.0%(95%CI，19%至43%)(HR，0.63；95%CI，0.41至0.98；P=.043)。RFS的增加可能与Clara组比HDAC组观察到的较低的累积复发率有关(2年时分别为33.9%对46.4%；特定原因的HR，0.61；95%CI，0.40至0.94；P=.025)。与HDAC周期相比，Clara周期具有更高的血液学和非血液学毒性。结论这些结果提示Clara周期可能被考虑作为首次缓解的年轻AML患者的一种新的化疗方案。(C)2017年美国临床肿瘤学会
PurposeTo evaluate the efficacy and safety of a clofarabine-based combination (CLARA) versus conventional high-dose cytarabine (HDAC) as postremission chemotherapy in younger patients with acute myeloid leukemia (AML).Patients and MethodsPatients age 18 to 59 years old with intermediate-or unfavorable-risk AML in first remission and no identified donor for allogeneic stem-cell transplantation (SCT) were eligible. Two hundred twenty-one patients were randomly assigned to receive three CLARA or three HDAC consolidation cycles. The primary end point was relapse-free survival (RFS). To handle the confounding effect of SCT that could occur in patients with late donor identification, hazard ratios (HRs) of events were adjusted on the time-dependent treatment 3 SCT interaction term.ResultsAt 2 years, RFS was 58.5% (95% CI, 49% to 67%) in the CLARA arm and 46.5% (95% CI, 37% to 55%) in the HDAC arm. Overall, 110 patients (55 in each arm) received SCT in first remission. On the basis of a multivariable Cox-adjusted treatment 3 SCT interaction, the HR of CLARA over HDAC before or in absence of SCT was 0.65 (95% CI, 0.43 to 0.98; P = .041). In a sensitivity analysis, when patients who received SCT in first remission were censored at SCT time, 2-year RFS was 53.3% (95% CI, 39% to 66%) in the CLARA arm and 31.0% (95% CI, 19% to 43%) in the HDAC arm (HR, 0.63; 95% CI, 0.41 to 0.98; P = .043). Gain in RFS could be related to the lower cumulative incidence of relapse observed in the CLARA arm versus the HDAC arm (33.9% v 46.4% at 2 years, respectively; cause-specific HR, 0.61; 95% CI, 0.40 to 0.94; P = .025). CLARA cycles were associated with higher hematologic and nonhematologic toxicity than HDAC cycles.ConclusionThese results suggest that CLARA might be considered as a new chemotherapy option in younger patients with AML in first remission. (C) 2017 by American Society of Clinical Oncology