Laboratoire d'Hématologie, Centre Hospitalier Universitaire de Lille, and INSERM Unité 837, Lille, France.
N Engl J Med. 2010 Dec 23;363(26):2511-21. doi: 10.1056/NEJMoa1004095.
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.
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 μg 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(10) units or more from the baseline level, as assessed by means of a real-time quantitative polymerase-chain-reaction assay.
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.
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.).
伊马替尼（每天 400 毫克）被认为是新诊断的慢性髓性白血病（CML）慢性期患者的最佳初始治疗方法。然而，接受伊马替尼治疗的患者中只有少数人获得完全分子缓解。
我们将 636 例未经治疗的慢性期 CML 患者随机分为四组，分别接受每天 400 毫克的伊马替尼单药治疗、每天 400 毫克的伊马替尼加阿糖胞苷（每 28 天周期的第 15 至 28 天每天每平方米体表面积 20 毫克）或聚乙二醇干扰素（peginterferon） alfa-2a（每周 90μg），或每天 600 毫克的伊马替尼单药治疗。评估分子和细胞遗传学反应、治疗失败时间、总生存率和无事件生存率以及不良事件。计划进行 12 个月的分子反应分析。优异的分子反应定义为酪氨酸激酶基因 BCR-ABL 与 ABL 转录物的比值下降 0.01%或更低，与基线相比降低 4 个对数（10）单位或更多，通过实时定量聚合酶链反应检测。
在 12 个月时，四组患者的细胞遗传学反应率相似。接受伊马替尼和 peginterferon alfa-2a 治疗的患者的优异分子反应率（30%）明显高于接受 400 毫克伊马替尼单药治疗的患者（14%）（P=0.001）。治疗时间超过 12 个月的患者显著高于治疗 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事件更频繁，而接受 peginterferon alfa-2a 治疗的患者皮疹和抑郁更频繁。
与其他治疗方法相比，伊马替尼联合 peginterferon alfa-2a 治疗可显著提高慢性期 CML 患者的分子反应率。（由法国卫生部等资助；ClinicalTrials.gov 编号，NCT00219739）。
