Alemtuzumab compared with chlorambucil as first-line therapy for chronic lymphocytic leukemia
Alemtuzumab compared with chlorambucil as first-line therapy for chronic lymphocytic leukemia
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DOI：
10.1200/jco.2007.12.9098
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发表时间：
2007-12-10
影响因子：
45.3
通讯作者：
Mayer, Jiri
中科院分区：
文献类型：
--
作者：
Hillmen, Peter;Skotnicki, Aleksander B.;Mayer, Jiri
PurposeWe进行了一项随机试验，以评估静脉注射阿仑单抗与苯丁酸氮芥相比，在慢性淋巴细胞白血病（CLL.Patients and MethodsPatients）一线治疗中的疗效和安全性。主要终点是无进展生存期（PFS）。次要终点包括总反应率（ORR），完全反应（CR），替代疗法的时间，安全性和总survival.ResultsWe随机分配297例患者，149阿仑单抗和148苯丁酸氮芥。Alemtuzumab的PFS上级，进展或死亡风险降低42%（风险比[ HR] = 0.58; P = .0001），至替代治疗的中位时间为23.3个月，而苯丁酸氮芥为14.7个月（HR = 0.54; P = .0001）。Alemtuzumab组的ORR为83%（24% CR），而苯丁酸氮芥组为55%（2% CR）; ORR和CR的差异具有高度统计学意义（P < .0001）。在36例Alemtuzumab完全应答者中，11例发生微小残留病消除，而苯丁酸氮芥无。不良事件特征相似，但阿仑单抗组输注相关和巨细胞病毒（CMV）事件较多，苯丁酸氮芥组恶心和呕吐较多。CMV事件对疗效无明显影响。ConclusionAs一线治疗CLL患者，阿仑单抗显示与苯丁酸氮芥相比，显著改善PFS，替代治疗时间，ORR和CR，以及最小的残留疾病阴性缓解，具有可预测和可管理的毒性。
PurposeWe conducted a randomized trial to evaluate the efficacy and safety of intravenous alemtuzumab compared with chlorambucil in first-line treatment of chronic lymphocytic leukemia (CLL).Patients and MethodsPatients received alemtuzumab (30 mg three times per week, for up to 12 weeks) or chlorambucil (40 mg/m(2) every 28 days, for up to 12 months). The primary end point was progression-free survival (PFS). Secondary end points included overall response rate (ORR), complete response (CR), time to alternative therapy, safety, and overall survival.ResultsWe randomly assigned 297 patients, 149 to alemtuzumab and 148 to chlorambucil. Alemtuzumab had superior PFS, with a 42% reduction in risk of progression or death (hazard ratio [ HR] = 0.58; P = .0001), and a median time to alternative treatment of 23.3 versus 14.7 months for chlorambucil (HR = 0.54; P = .0001). The ORR was 83% with alemtuzumab (24% CR) versus 55% with chlorambucil (2% CR); differences in ORR and CR were highly statistically significant (P < .0001). Elimination of minimal residual disease occurred in 11 of 36 complete responders to alemtuzumab versus none to chlorambucil. Adverse events profiles were similar, except for more infusion-related and cytomegalovirus (CMV) events with alemtuzumab and more nausea and vomiting with chlorambucil. CMV events had no apparent impact on efficacy.ConclusionAs first-line treatment for patients with CLL, alemtuzumab demonstrated significantly improved PFS, time to alternative treatment, ORR and CR, and minimal residual disease-negative remissions compared with chlorambucil, with predictable and manageable toxicity.