Rituximab versus a watch-and-wait approach in patients with advanced- stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial
Rituximab versus a watch-and-wait approach in patients with advanced- stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial
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DOI：
10.1016/s1470-2045(14)70027-0
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发表时间：
2014-04-01
期刊：
影响因子：
51.1
通讯作者：
Linch, David C.
中科院分区：
文献类型：
--
作者：
Ardeshna, Kirit M.;Qian, Wendi;Linch, David C.
背景：晚期低肿瘤负荷滤泡性淋巴瘤患者通常需要观察等待疾病进展。我们评估了与观察等待相比，使用利妥昔单抗是否可以延迟化疗或放疗的需要，以及这种策略对生活质量（QoL）的影响。（年龄>= 18岁）低肿瘤负荷滤泡性淋巴瘤（1、2和3a级）随机集中分配（1：1：1），通过按机构、年级、阶段和年龄艾德的最小化方法，到警惕等待，利妥昔单抗375 mg/m2，每周一次，持续4周（利妥昔单抗诱导），或利妥昔单抗诱导后，每隔2个月再输注12次，持续2年（利妥昔单抗维持）。2007年9月30日，利妥昔单抗诱导组的招募结束，研究修改为两组研究。主要终点为至开始新治疗的时间和第7个月（即利妥昔单抗诱导治疗完成后6个月）的QoL。所有随机分配的患者均纳入至开始新治疗的时间分析（基于意向治疗）。主要研究现已完成，正在进行长期随访。该研究注册于ClinicalTrials.gov，NCT 00112931。结果2004年10月15日至2009年3月25日，来自英国、澳大利亚、新西兰、土耳其和波兰118个中心的379名患者被随机分配到观察等待或维持利妥昔单抗组。84名患者在早期关闭之前被招募到利妥昔单抗诱导组。在开始新治疗的时间上存在显著差异，观察等待组中46%（95%CI 39-53）的患者在3年时不需要治疗，而维持利妥昔单抗组中88%（83-92）的患者在3年时不需要治疗（风险比[HR] 0.21，95%CI 0.14 -0.31; p
Background Patients with advanced-stage, low-tumour-burden follicular lymphoma have conventionally undergone watchful waiting until disease progression. We assessed whether rituximab use could delay the need for chemotherapy or radiotherapy compared with watchful waiting and the effect of this strategy on quality of life (QoL).Methods Asymptomatic patients (aged >= 18 years) with low-tumour-burden follicular lymphoma (grades 1, 2, and 3a) were randomly assigned centrally (1:1:1), by the minimisation approach stratifi ed by institution, grade, stage, and age, to watchful waiting, rituximab 375 mg/m(2) weekly for 4 weeks (rituximab induction), or rituximab induction followed by a maintenance schedule of 12 further infusions given at 2-monthly intervals for 2 years (maintenance rituximab). On Sept 30, 2007, recruitment into the rituximab induction group was closed and the study was amended to a two-arm study. The primary endpoints were time to start of new treatment and QoL at month 7 (ie, 6 months after completion of rituximab induction). All randomly assigned patients were included in the analysis of time to start of new treatment on an intention-to-treat basis. The main study is now completed and is in long-term follow-up. The study is registered with ClinicalTrials.gov, NCT00112931.Findings Between Oct 15, 2004, and March 25, 2009, 379 patients from 118 centres in the UK, Australia, New Zealand, Turkey, and Poland were randomly assigned to watchful waiting or maintenance rituximab. 84 patients were recruited to the rituximab induction group before it was closed early. There was a significant difference in the time to start of new treatment, with 46% (95% CI 39-53) of patients in the watchful waiting group not needing treatment at 3 years compared with 88% (83-92) in the maintenance rituximab group (hazard ratio [HR] 0 .21, 95% CI 0 .14-0.31; p