Imatinib plus Peginterferon Alfa-2a in Chronic Myeloid Leukemia.
Imatinib plus Peginterferon Alfa-2a in Chronic Myeloid Leukemia.
复制标题
DOI：
10.1056/nejmoa1004095
复制
发表时间：
2010-12-23
影响因子：
158.5
通讯作者：
Guilhot, Francois
中科院分区：
文献类型：
--
作者：
Preudhomme, Claude;Guilhot, Joelle;Guilhot, Francois
背景：伊马替尼(400 mg/d)被认为是新诊断的慢性粒细胞白血病(CML)慢性期患者的最佳初始治疗方案。然而，只有少数接受伊马替尼治疗的患者完全分子缓解。方法：我们随机将636例未经治疗的慢性期CML患者分为三组，分别接受伊马替尼400 mg/d、伊马替尼400 mg/d加阿糖胞苷20 mg/m2，每平方米每天20 mg，或聚乙二醇化干扰素(聚乙二醇化干扰素)α-2a(每周90微克)，或单用伊马替尼600 mg/d。评估了分子和细胞遗传学反应、治疗失败的时间、总体和无事件生存期以及不良事件。计划在12个月时进行分子反应分析。通过实时定量聚合酶链式反应分析，较好的分子反应定义为酪氨酸激酶基因bcr-abl的转录本与abl的转录本的比率降低0.01%或更少，相当于从基线水平减少4log(Sub10)单位或更多。结果：12个月时，四组患者的细胞遗传学反应率相似。在接受伊马替尼和聚乙二醇干扰素α-2a治疗的患者中，分子反应率(30%)显著高于仅接受400mg伊马替尼治疗的患者(14%)(P=0.001)。在接受治疗12个月以上的患者中，这一比例明显高于接受治疗12个月或更短时间的患者。接受阿糖胞苷治疗的患者胃肠道反应更常见，而接受聚乙二醇干扰素α-2a治疗的患者更容易出现皮疹和抑郁。结论：与其他治疗方法相比，在伊马替尼治疗的基础上加用聚乙二醇干扰素α-2a治疗慢性期CML患者的分子应答率显著提高。(由法国卫生部和其他机构资助；ClinicalTrials.gov编号，NCT00219739。)N Engl J Med 2010；363：2511-21。
Background: Imatinib (400 mg daily) is considered the best initial therapy for patients with newly diagnosed chronic myeloid leukemia (CML) in the chronic phase. However, only a minority of patients treated with imatinib have a complete molecular remission.Methods: We randomly assigned 636 patients with untreated chronic-phase CML to receive imatinib alone at a dose of 400 mg daily, imatinib (400 mg daily) plus cytarabine (20 mg per square meter of body-surface area per day on days 15 through 28 of each 28-day cycle) or pegylated interferon (peginterferon) alfa-2a (90 microg weekly), or imatinib alone at a dose of 600 mg daily. Molecular and cytogenetic responses, time to treatment failure, overall and event-free survival, and adverse events were assessed. An analysis of molecular response at 12 months was planned. A superior molecular response was defined as a decrease in the ratio of transcripts of the tyrosine kinase gene BCR-ABL to transcripts of ABL of 0.01% or less, corresponding to a reduction of 4 log(sub 10) units or more from the baseline level, as assessed by means of a real-time quantitative polymerase-chain-reaction assay.Results: At 12 months, the rates of cytogenetic response were similar among the four groups. The rate of a superior molecular response was significantly higher among patients receiving imatinib and peginterferon alfa-2a (30%) than among patients receiving 400 mg of imatinib alone (14%) (P=0.001). The rate was significantly higher among patients treated for more than 12 months than among those treated for 12 months or less. Gastrointestinal events were more frequent among patients receiving cytarabine, whereas rash and depression were more frequent among patients receiving peginterferon alfa-2a.Conclusions: As compared with other treatments, the addition of peginterferon alfa-2a to imatinib therapy resulted in significantly higher rates of molecular response in patients with chronic-phase CML. (Funded by the French Ministry of Health and others; ClinicalTrials.gov number, NCT00219739.)N Engl J Med 2010;363:2511-21.