Therapeutic value of clofarabine in younger and middle-aged (18-65 years) adults with newly diagnosed AML
Therapeutic value of clofarabine in younger and middle-aged (18-65 years) adults with newly diagnosed AML
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DOI：
10.1182/blood-2016-10-740613
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发表时间：
2017-03-23
期刊：
影响因子：
20.3
通讯作者：
Ossenkoppele, Gert J.
中科院分区：
文献类型：
--
作者：
Lowenberg, Bob;Pabst, Thomas;Ossenkoppele, Gert J.
氯法拉滨已在急性髓系白血病(AML)中显示出抗白血病活性，但尚未对处于标准化疗一线的年轻人进行严格评估。我们比较了两种诱导方案对18~65岁新诊断的急性髓系白血病(AML)/高危骨髓增生异常综合征患者，即阿糖胞苷-阿糖胞苷(周期I)和阿马西林-阿糖胞苷(周期II)单独或联合氯法拉滨(10 mg/m2，每周期1-5天)。巩固包括使用或不使用造血干细胞移植的化疗。无事件生存率(EFS，主要终点)和其他临床终点和毒性进行了评估。我们将402名和393名可评估的患者随机分为对照组或氯法拉滨诱导治疗组。完全缓解率(89%)无差异，但氯法拉滨的完全缓解率(66%)更快(I周期后为75%)。氯法拉滨增加了3至4级毒性，并延迟了血液学恢复。在平均36个月的随访中，这项研究显示，对照组(4年EFS，35%63[标准误])和氯法拉滨治疗组(38%+/-3)在总体存活率和EFS方面没有差异，但氯法拉滨治疗组的复发率显著降低(44%+/-3vs35%+/-3)，缓解期死亡概率增加(15%+/-2vs22%+/-3)。在亚组分析中，氯法拉滨改善了欧洲白血病网络(ELN)2010年中期I期预后风险AML(4年EFS，26%+/-4vs40%+/-5；CoxP5.002)和没有内部串联重复的中危基因NPM1野生型/Flt3的总体生存率和EFS(EFS，18%+/-5vs40%+/-7；COX P
Clofarabine has demonstrated antileukemic activity in acute myeloid leukemia (AML) but has yet to be critically evaluated in younger adults in the frontline with standard chemotherapy. We compared 2 induction regimens in newly diagnosed patients ages 18 to 65 with acute myeloid leukemia (AML)/high-risk myelodysplastic syndromes, that is, idarubicine-cytarabine (cycle I) and amsacrine-cytarabine (cycle II) without or with clofarabine (10 mg/m 2 on days 1-5 of each of both cycles). Consolidation involved chemotherapy with or without hematopoietic stem cell transplantation. Event-free survival (EFS, primary endpoint) and other clinical endpoints and toxicities were assessed. We randomized 402 and 393 evaluable patients to the control or clofarabine induction treatment arms. Complete remission rates (89%) did not differ but were attained faster with clofarabine (66% vs 75% after cycle I). Clofarabine added grades 3 to 4 toxicities and delayed hematological recovery. At a median follow-up of 36 months, the study revealsnodifferences in overall survival and EFS between the control (EFS, 35% 63 [ standard error] at 4 years) and clofarabine treatments (38% +/- 3) but a markedly reduced relapse rate (44% +/- 3 vs 35% +/- 3) in favor of clofarabine and an increased death probability in remission (15% +/- 2 vs 22% +/- 3). In the subgroup analyses, clofarabine improved overall survival and EFS for European Leukemia Net (ELN) 2010 intermediate I prognostic riskAML(EFS, 26% +/- 4 vs40% +/- 5 at 4 years; CoxP5.002) and for the intermediate risk genotype NPM1 wild-type/FLT3 without internal-tandem duplications (EFS, 18% +/- 5 vs 40% +/- 7; Cox P