Multivariate and subgroup analyses of a randomized, multinational, phase 3 trial of decitabine vs treatment choice of supportive care or cytarabine in older patients with newly diagnosed acute myeloid leukemia and poor- or intermediate-risk cytogenetics.
Multivariate and subgroup analyses of a randomized, multinational, phase 3 trial of decitabine vs treatment choice of supportive care or cytarabine in older patients with newly diagnosed acute myeloid leukemia and poor- or intermediate-risk cytogenetics.
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DOI：
10.1186/1471-2407-14-69
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发表时间：
2014-02-06
期刊：
影响因子：
3.8
通讯作者：
Kantarjian HM
中科院分区：
文献类型：
--
作者：
Mayer J;Arthur C;Delaunay J;Mazur G;Thomas XG;Wierzbowska A;Ravandi F;Berrak E;Jones M;Li Y;Kantarjian HM
与年轻患者相比，患有急性髓系白血病（AML）的老年人的生存结局通常较差，并且从临床试验中获益较少。最近的一项3期试验显示，与阿糖胞苷或支持性治疗相比，地西他滨（一种低甲基化药物）在新诊断的AML老年人中有改善总生存期（OS）的趋势（分别为7.7个月，95% CI：6.2-9.2 vs 5.0个月，95% CI：4.3-6.3）。当前分析研究了本试验结局的预后因素，并检查了预先指定亚组的OS和缓解。基于成熟数据，使用多变量考克斯比例风险模型研究人口统计学和基线特征（包括年龄、性别、细胞遗传学风险、AML类型、ECOG体能状态、地理区域、骨髓原始细胞、血小板和白色血细胞）对OS的影响。采用逻辑回归模型进行类似分析，以预测缓解率。还使用成熟数据对OS和缓解率进行了预先规定的亚组分析。似乎对OS产生负面影响的患者特征包括年龄较大（≥75岁vs <70岁的风险比[HR] 1.560; p = 0.0010），基线时体能状态较差（HR 0.771，0或1 vs 2; p = 0.0321），细胞遗传学较差（中度vs差的HR 0.699; p = 0.0010），骨髓原始细胞计数较高（HR 1.355，>50% vs ≤50%; p = 0.0045），基线血小板计数低（每增加100 × 109/L，HR 0.775; p = 0.0015）和高白色血细胞计数（每增加25 × 109/L，HR 1.256; p = 0.0151）。关于地理区域，西欧患者的中位OS最长。在所有研究的亚组中，包括≥75岁的患者，缓解率均有利于地西他滨（比值比5.94，p = 0.0006）。AML患者对地西他滨的反应与已知的与患者人口统计学和疾病特征相关的预后因素相关。ClinicalTrials.gov标识符NCT 00260832
Compared with younger patients, older adults with acute myeloid leukemia (AML) generally have poorer survival outcomes and less benefit from clinical trials. A recent phase 3 trial demonstrated a trend toward improved overall survival (OS) with decitabine, a hypomethylating agent, compared with treatment choice of either cytarabine or supportive care (7.7 months, 95% CI: 6.2–9.2 vs 5.0 months, 95% CI: 4.3–6.3, respectively) in older adults with newly diagnosed AML. The current analyses investigated prognostic factors for outcomes in this trial and examined OS and responses in prespecified subgroups. A multivariate Cox proportional hazards model was used to investigate effects of demographic and baseline characteristics, including age, sex, cytogenetic risk, AML type, ECOG Performance Status, geographic region, bone marrow blasts, platelets, and white blood cells on OS, based on mature data. Similar analyses were conducted with a logistic regression model to predict response rates. Prespecified subgroup analyses were performed for OS and response rates, also using mature data. Patient characteristics that appeared to negatively influence OS included more advanced age (hazard ratio [HR] 1.560 for ≥75 vs <70 years; p = 0.0010), poorer performance status at baseline (HR 0.771 for 0 or 1 vs 2; p = 0.0321), poor cytogenetics (HR 0.699 for intermediate vs poor; p = 0.0010), higher bone marrow blast counts (HR 1.355 for >50% vs ≤50%; p = 0.0045), low baseline platelet counts (HR 0.775 for each additional 100 × 109/L; p = 0.0015), and high white blood cell counts (HR 1.256 for each additional 25 × 109/L; p = 0.0151). Regarding geographic regions, patients from Western Europe had the longest median OS. Response rates favored decitabine for all subgroups investigated, including patients ≥75 years (odds ratio 5.94, p = 0.0006). Response to decitabine in AML is associated with known prognostic factors related to both patient demographics and disease characteristics. ClinicalTrials.gov identifier NCT00260832
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影响因子：
6.2
作者：
Kantarjian, H;O'Brien, S;Estey, E
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45.3
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