Individual patient data meta-analysis of randomized trials evaluating IL-2 monotherapy as remission maintenance therapy in acute myeloid leukemia
Individual patient data meta-analysis of randomized trials evaluating IL-2 monotherapy as remission maintenance therapy in acute myeloid leukemia
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DOI：
10.1182/blood-2011-02-337725
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发表时间：
2011-06-30
期刊：
影响因子：
20.3
通讯作者：
Burzykowski, Tomasz
中科院分区：
文献类型：
--
作者：
Buyse, Marc;Squifflet, Pierre;Burzykowski, Tomasz
IL-2是天然的T细胞衍生的细胞因子，其刺激T细胞和自然杀伤细胞的细胞毒性功能。在几项随机临床试验（RCT）中对IL-2单药治疗在急性髓性白血病（AML）患者首次完全缓解（CR 1）中的缓解维持进行了评价，但没有一项显示IL-2单药治疗的显著获益。该荟萃分析的目的是通过结合5项RCT（N = 905）的所有可用个体患者数据（IPD）和第6项RCT（N = 550）的汇总数据，可靠地确定IL-2的疗效。使用按试验分层的考克斯回归模型估计风险比（HR），HR < 1表示治疗获益。在无白血病生存期（HR = 0.97; P = 0.74）或总生存期（HR = 1.08; P = 0.39）方面，联合IPD显示IL-2治疗与未治疗相比无任何益处。包括第六项RCT在内的分析得出了定性相同的结果（无白血病生存期HR = 0.96，P = 0.52;总生存期HR = 1.06; P = 0.46）。试验间未发现显著异质性。预先设定的亚组分析显示，缺乏IL-2效应与任何因素（包括年龄、性别、基线体能状态、核型、AML亚型和从达到CR 1至开始维持治疗的时间）之间无相互作用。我们的结论是，IL-2单独是不是一个有效的缓解维持治疗AML患者CR 1。（血。2011;117（26）：7007-7013）
IL-2 is a natural, T cell-derived cytokine that stimulates the cytotoxic functions of T and natural killer cells. IL-2 monotherapy has been evaluated in several randomized clinical trials (RCTs) for remission maintenance in patients with acute myeloid leukemia (AML) in first complete remission (CR1), and none demonstrated a significant benefit of IL-2 monotherapy. The objective of this meta-analysis was to reliably determine IL-2 efficacy by combining all available individual patient data (IPD) from 5 RCTs (N = 905) and summary data from a sixth RCT (N = 550). Hazard ratios (HRs) were estimated using Cox regression models stratified by trial, with HR < 1 indicating treatment benefit. Combined IPD showed no benefit of IL-2 over no treatment in terms of leukemia-free survival (HR = 0.97; P = .74) or overall survival (HR = 1.08; P = .39). Analyses including the sixth RCT yielded qualitatively identical results (leukemia-free survival HR = 0.96, P = .52; overall survival HR = 1.06; P = .46). No significant heterogeneity was found between the trials. Prespecified subset analyses showed no interaction between the lack of IL-2 effect and any factor, including age, sex, baseline performance status, karyotype, AML subtype, and time from achievement of CR1 to initiation of maintenance therapy. We conclude that IL-2 alone is not an effective remission maintenance therapy for AML patients in CR1. (Blood. 2011;117(26):7007-7013)