Favorable long-term follow-up results over 6 years for response, survival, and safety with imatinib mesylate therapy in chronic-phase chronic myeloid leukemia after failure of interferon-α treatment
Favorable long-term follow-up results over 6 years for response, survival, and safety with imatinib mesylate therapy in chronic-phase chronic myeloid leukemia after failure of interferon-α treatment
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DOI：
10.1182/blood-2007-07-103523
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发表时间：
2008-02-01
期刊：
影响因子：
20.3
通讯作者：
Kantarjian, Hagop M.
中科院分区：
文献类型：
--
作者：
Hochhaus, Andreas;Druker, Brian;Kantarjian, Hagop M.
甲磺酸伊马替尼是BCR-ABL酪氨酸激酶的靶向抑制剂，是慢性髓性白血病（CML）的标准治疗药物。一项伊马替尼治疗干扰素- A （IFN α）失败后晚期慢性粒细胞白血病（CP）的2期试验纳入了532例患者，其中454例确诊为CP CML。中位诊断时间为34个月；伊马替尼治疗的中位持续时间为65个月。累积最佳主要细胞遗传学缓解率（MCyR）和完全细胞遗传学缓解率（CCyR）分别为67%和57%。在5年里程碑时，454例患者中有184例（41%）处于CCyR。在超过6年的时间里，454名患者中有199名（44%）仍在使用伊马替尼。大多数反应发生在开始使用伊马替尼的12个月内；然而，一些患者在伊马替尼开始治疗后超过5年才达到初始MCyR和CCyR。估计从进展到加速期（AP）和成胚期（BP）的自由率和6年总生存率分别为61%和76%。无进展到AP/BP和总生存期（OS）与12个月时的细胞遗传学反应水平相关。与早期时间点相比，连续使用伊马替尼6.5年未观察到严重不良事件发生率的增加。对于干扰素治疗失败后的CP CML患者，伊马替尼仍然是一种有效和安全的治疗方法。
Imatinib mesylate, a targeted inhibitor of BCR-ABL tyrosine kinase, is the standard of care for chronic myeloid leukemia (CML). A phase 2 trial of imatinib in late chronic-phase (CP) CML after interferon-a (IFN alpha) failure enrolled 532 patients, 454 with a confirmed diagnosis of CP CML. Median time from diagnosis was 34 months; median duration of imatinib treatment was 65 months. Cumulative best rates of major cytogenetic response (MCyR) and complete cytogenetic response (CCyR) were 67% and 57%, respectively. At the 5-year landmark, 184 (41 %) of the 454 patients are in CCyR. At more than 6 years, 199 (44%) of the 454 patients remain on imatinib. Most responses occurred within 12 months of starting imatinib; however, some patients achieved initial MCyR and CCyR more than 5 years after imatinib initiation. Estimated rates of freedom from progression to accelerated phase (AP) and blastic phase (BP) and overall survival at 6 years were 61% and 76%, respectively. Both freedom from progression to AP/BP and overall survival (OS) were associated with cytogenetic response level at 12 months. No increase in rates of serious adverse events was observed with continuous use of imatinib for up to 6.5 years, compared with earlier time points. Imatinib continues to be an effective and safe therapy for patients with CP CML after failure of IFN.