Kantarjian Hagop, O'Brien Susan, Cortes Jorge, Giles Francis, Shan Jianqin, Rios Mary Beth, Faderl Stefan, Verstovsek Srdan, Garcia-Manero Guillermo, Wierda William, Kornblau Steven, Ferrajoli Alessandra, Keating Michael, Talpaz Moshe
Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):68-75. doi: 10.1158/1078-0432.ccr-1035-3.
The purpose of this research was to compare the survival of patients with Philadelphia chromosome (Ph) -positive chronic myelogenous leukemia (CML) post-IFN-alpha failure treated with imatinib to historical experiences with standards of care or other therapies.
The outcome of 261 patients with Ph-positive chronic phase CML post-IFN failure treated with imatinib was compared with 204 historical control patients treated for a similar disease status with existing therapies. A subset of 147 patients in late chronic phase CML and 100% Ph-positive status treated with imatinib was compared with 95 patients in a similar disease status treated with IFN. Multivariate analyses were conducted to assess the independent prognostic effect of therapy (imatinib versus other) on survival.
In the first analysis involving 261 patients on imatinib plus 204 historical patients, the complete cytogenetic response rates were 62% and 19%, respectively (P < 0.001). A multivariate analysis identified pretreatment peripheral blasts and thrombocytosis to be independent poor prognostic factors for survival. Imatinib therapy (versus others) was a significant independent favorable prognostic factor for survival (hazard ratio, 0.17; P < 0.0001). In the second analysis involving the subset of 147 patients receiving imatinib plus 95 historical patients treated with IFN regimens, the complete cytogenetic response rates were 41% and 7%, respectively (P < 0.001). A multivariate analysis selected pretreatment anemia and peripheral blasts to be significant independent poor prognostic factors for survival. Imatinib therapy (versus IFN) was an independent favorable prognostic factor for survival (hazard ratio, 0.20; P < 0.0001). Three-month and 6-month landmark analyses showed that patients in all cytogenetic response categories (major, minor, and none) after imatinib therapy had survival outcomes better than the historical control population. Within each cytogenetic response category, survival was also better with imatinib than with other therapies.
This analysis provides evidence for a survival advantage with imatinib versus other therapies in chronic-phase CML post-IFN failure, and for a survival advantage with imatinib versus IFN in late chronic-phase CML.
本研究旨在比较接受伊马替尼治疗的α干扰素治疗失败后的费城染色体（Ph）阳性慢性髓性白血病（CML）患者的生存率与采用标准治疗或其他疗法的历史经验。
将261例接受伊马替尼治疗的Ph阳性慢性期CML患者在干扰素治疗失败后的结果与204例接受现有疗法治疗的具有相似疾病状态的历史对照患者进行比较。将147例处于慢性期晚期且Ph阳性状态的CML患者接受伊马替尼治疗的亚组与95例处于相似疾病状态的接受干扰素治疗的患者进行比较。进行多变量分析以评估治疗（伊马替尼与其他治疗）对生存率的独立预后影响。
在涉及261例接受伊马替尼治疗的患者和204例历史患者的首次分析中，完全细胞遗传学缓解率分别为62%和19%（P < 0.001）。多变量分析确定治疗前外周血原始细胞和血小板增多是生存率的独立不良预后因素。伊马替尼治疗（与其他治疗相比）是生存率的显著独立有利预后因素（风险比，0.17；P < 0.0001）。在涉及147例接受伊马替尼治疗的患者亚组和95例接受干扰素方案治疗的历史患者的第二次分析中，完全细胞遗传学缓解率分别为41%和7%（P < 0.001）。多变量分析选择治疗前贫血和外周血原始细胞作为生存率的显著独立不良预后因素。伊马替尼治疗（与干扰素相比）是生存率的独立有利预后因素（风险比，0.20；P < 0.0001）。3个月和6个月的标志性分析表明，伊马替尼治疗后所有细胞遗传学缓解类别（主要、次要和无缓解）的患者的生存结果均优于历史对照人群。在每个细胞遗传学缓解类别中，伊马替尼治疗的患者的生存率也高于其他疗法。
本分析提供了证据，表明在干扰素治疗失败后的慢性期CML中，伊马替尼治疗与其他疗法相比具有生存优势，并且在慢性期晚期CML中，伊马替尼治疗与干扰素相比具有生存优势。
