伊马替尼治疗慢性髓性白血病的长期疗效
Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia.
作者信息
Hochhaus Andreas, Larson Richard A, Guilhot François, Radich Jerald P, Branford Susan, Hughes Timothy P, Baccarani Michele, Deininger Michael W, Cervantes Francisco, Fujihara Satoko, Ortmann Christine-Elke, Menssen Hans D, Kantarjian Hagop, O'Brien Stephen G, Druker Brian J
机构信息
From Abteilung Hämatologie-Onkologie, Universitätsklinikum Jena, Jena, Germany (A.H.); the Department of Medicine, University of Chicago, Chicago (R.A.L.); INSERM Centre d'Investigation Clinique 1402, Centre Hospitalier Universitaire de Poitiers, Poitiers, France (F.G.); Fred Hutchinson Cancer Research Center, Seattle (J.P.R.); Centre for Cancer Biology, SA Pathology, University of South Australia and University of Adelaide (S.B.), and the South Australian Health and Medical Research Institute and University of Adelaide (T.P.H.), Adelaide, SA, Australia; University of Bologna, Bologna, Italy (M.B.); the University of Utah Huntsman Cancer Institute, Salt Lake City (M.W.D.); the Hematology Department, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona (F.C.); Novartis, Basel, Switzerland (S.F., C.-E.O., H.D.M.); M.D. Anderson Cancer Center, Houston (H.K.); the University of Newcastle, Newcastle, United Kingdom (S.G.O.); and Knight Cancer Institute, Oregon Health and Science University and Howard Hughes Medical Institute, Portland (B.J.D.).
出版信息
N Engl J Med. 2017 Mar 9;376(10):917-927. doi: 10.1056/NEJMoa1609324.
BACKGROUND
Imatinib, a selective BCR-ABL1 kinase inhibitor, improved the prognosis for patients with chronic myeloid leukemia (CML). We conducted efficacy and safety analyses on the basis of more than 10 years of follow-up in patients with CML who were treated with imatinib as initial therapy.
METHODS
In this open-label, multicenter trial with crossover design, we randomly assigned patients with newly diagnosed CML in the chronic phase to receive either imatinib or interferon alfa plus cytarabine. Long-term analyses included overall survival, response to treatment, and serious adverse events.
RESULTS
The median follow-up was 10.9 years. Given the high rate of crossover among patients who had been randomly assigned to receive interferon alfa plus cytarabine (65.6%) and the short duration of therapy before crossover in these patients (median, 0.8 years), the current analyses focused on patients who had been randomly assigned to receive imatinib. Among the patients in the imatinib group, the estimated overall survival rate at 10 years was 83.3%. Approximately half the patients (48.3%) who had been randomly assigned to imatinib completed study treatment with imatinib, and 82.8% had a complete cytogenetic response. Serious adverse events that were considered by the investigators to be related to imatinib were uncommon and most frequently occurred during the first year of treatment.
CONCLUSIONS
Almost 11 years of follow-up showed that the efficacy of imatinib persisted over time and that long-term administration of imatinib was not associated with unacceptable cumulative or late toxic effects. (Funded by Novartis Pharmaceuticals; IRIS ClinicalTrials.gov numbers, NCT00006343 and NCT00333840 .).
背景
伊马替尼是一种选择性BCR-ABL1激酶抑制剂，改善了慢性髓性白血病（CML）患者的预后。我们基于对接受伊马替尼初始治疗的CML患者超过10年的随访进行了疗效和安全性分析。
方法
在这项采用交叉设计的开放标签多中心试验中，我们将新诊断为慢性期CML的患者随机分配接受伊马替尼或干扰素α加阿糖胞苷治疗。长期分析包括总生存期、治疗反应和严重不良事件。
结果
中位随访时间为10.9年。鉴于随机分配接受干扰素α加阿糖胞苷治疗的患者交叉率较高（65.6%），且这些患者在交叉前的治疗持续时间较短（中位时间为0.8年），当前分析聚焦于随机分配接受伊马替尼治疗的患者。在伊马替尼组患者中，10年时的估计总生存率为83.3%。随机分配接受伊马替尼治疗的患者中约一半（48.3%）完成了伊马替尼的研究治疗，82.8%的患者获得了完全细胞遗传学反应。研究人员认为与伊马替尼相关的严重不良事件并不常见，且最常发生在治疗的第一年。
结论
近11年的随访表明，伊马替尼的疗效随时间持续存在，长期使用伊马替尼与不可接受的累积或晚期毒性作用无关。（由诺华制药公司资助；IRIS临床试验.gov编号，NCT00006343和NCT00333840。）
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