Identification of Patients With Acute Myeloblastic Leukemia Who Benefit From the Addition of Gemtuzumab Ozogamicin: Results of the MRC AML15 Trial
Identification of Patients With Acute Myeloblastic Leukemia Who Benefit From the Addition of Gemtuzumab Ozogamicin: Results of the MRC AML15 Trial
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DOI：
10.1200/jco.2010.31.4310
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发表时间：
2011-02-01
影响因子：
45.3
通讯作者：
Wheatley, Keith
中科院分区：
文献类型：
--
作者：
Burnett, Alan K.;Hills, Robert K.;Wheatley, Keith
目的急性髓系白血病（AML）的抗体导向化疗可能允许更多的治疗，而不会增加毒性。吉妥珠单抗（GO）是CD 33和加利车霉素之间的免疫缀合物，其在与表位结合时被内化。我们先前已证实联合收割机GO与常规化疗联合是可行的。我们现在报告了一项大型随机试验，在未经治疗的年轻患者中，在诱导和/或巩固化疗中加入GO，患者和方法在这项开放标签试验中，1，113名患者，主要年龄小于60岁，被随机分配接受单剂量GO（3 mg/m2）在诱导疗程1的第1天使用以下三种诱导方案之一：柔红霉素和阿糖胞苷;阿糖胞苷、柔红霉素和依托泊苷;或氟达拉滨、阿糖胞苷、粒细胞集落刺激因子和依达拉滨。在缓解期，948例患者被随机分配到第3疗程的GO联合安吖啶、阿糖胞苷和依托泊苷或大剂量阿糖胞苷。主要终点反应率和survival.ResultsThe除了GO耐受性良好，没有显着增加毒性。在两种巩固诱导中，反应或生存率没有总体差异。然而，通过细胞遗传学进行的预定义分析显示与诱导GO具有高度显著的相互作用（P = .001），对于具有有利细胞遗传学的患者具有显著的生存益处，对于具有低风险疾病的患者没有益处，并且在中等风险患者中具有益处的趋势。一个内部验证的预后指数确定了约70%的患者的预测效益为10%，在5年survival.ConclusionA相当大比例的年轻AML患者的生存率提高了除了GO诱导化疗，几乎没有额外的毒性。J Clin Oncol 29：369-377. (c)2010年美国临床肿瘤学会
PurposeAntibody-directed chemotherapy for acute myeloid leukemia (AML) may permit more treatment to be administered without escalating toxicity. Gemtuzumab ozogamicin (GO) is an immunoconjugate between CD33 and calicheamicin that is internalized when binding to the epitope. We previously established that it is feasible to combine GO with conventional chemotherapy. We now report a large randomized trial testing the addition of GO to induction and/or consolidation chemotherapy in untreated younger patients.Patients and MethodsIn this open-label trial, 1,113 patients, predominantly younger than age 60 years, were randomly assigned to receive a single dose of GO (3 mg/m(2)) on day 1 of induction course 1 with one of the following three induction schedules: daunorubicin and cytarabine; cytarabine, daunorubicin, and etoposide; or fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin. In remission, 948 patients were randomly assigned to GO in course 3 in combination with amsacrine, cytarabine, and etoposide or high-dose cytarabine. The primary end points were response rate and survival.ResultsThe addition of GO was well tolerated with no significant increase in toxicity. There was no overall difference in response or survival in either induction of consolidation. However, a predefined analysis by cytogenetics showed highly significant interaction with induction GO (P = .001), with significant survival benefit for patients with favorable cytogenetics, no benefit for patients with poor-risk disease, and a trend for benefit in intermediate-risk patients. An internally validated prognostic index identified approximately 70% of patients with a predicted benefit of 10% in 5-year survival.ConclusionA substantial proportion of younger patients with AML have improved survival with the addition of GO to induction chemotherapy with little additional toxicity. J Clin Oncol 29: 369-377. (c) 2010 by American Society of Clinical Oncology