Early rituximab monotherapy versus watchful waiting for advanced stage, asymptomatic, low tumour burden follicular lymphoma: long-term results of a randomised, phase 3 trial.

Given the long natural history of follicular lymphoma, the trial was extended to further assess TTNT with longer follow-up.

鉴于滤泡性淋巴瘤的自然病程较长，试验延长以进一步评估更长随访时间下的TTNT。

Mature data are presented here.

这里我们展示了成熟的数据。

Methods

In this open-label, randomised, phase 3 trial, conducted at 118 centres in five countries, adult patients with asymptomatic, stage II-IV, grade 1-3a low tumour burden follicular lymphoma and Eastern Cooperative Oncology Group performance status 0-1 were randomly assigned (1:1:1) between watchful waiting, rituximab induction (375 mg/m2, intravenous) weekly for four doses (rituximab induction group) and rituximab induction followed by rituximab maintenance at the same dose every 8 weeks for 12 doses (rituximab maintenance group).

在这项开放标签、随机、第三阶段的试验中，共在五个国家的118个中心进行，研究对象为无症状、II-IV期、1-3a级低肿瘤负荷的滤泡性淋巴瘤成年患者，以及东协作肿瘤学组表现状态为0-1的患者。这些患者被随机分配（1:1:1）接受观察等待、利妥昔单抗诱导治疗（375 mg/m2，静脉注射），每周一次，连续四次（利妥昔单抗诱导组），以及利妥昔单抗诱导治疗后，以相同剂量每8周一次，连续12次的利妥昔单抗维持治疗（利妥昔单抗维持组）。

The rituximab induction group closed early on Sept 30, 2007, and the study was amended to a two-arm trial. The primary endpoint was TTNT, assessed in the intention-to-treatpopulation.

利妥昔单抗诱导组于2007年9月30日提前关闭，研究被修改为双臂试验。主要终点是TTNT，在意向治疗人群中进行评估。

The study is registered with ClinicalTrials.gov, NCT00112931, and recruitment and follow-up are complete.

该研究已在ClinicalTrials.gov注册，注册号为NCT00112931，招募和随访工作已完成。

Results

Between Oct 15, 2004, and May 1, 2009, 455 patients were randomly assigned, including 183 to watchful waiting, 82 to rituximab induction, and 190 to rituximab maintenance.

2004年10月15日至2009年5月1日期间，共有455名患者被随机分配，其中183名患者接受观察性等待，82名患者接受利妥昔单抗诱导治疗，190名患者接受利妥昔单抗维持治疗。

Median follow-up was 14·7 years (IQR 13·3-15·6).

中位随访时间为14.7年（四分位数间距13.3-15.6年）。

At 15 years, 65% (95% CI 56-72) of patients in the rituximab maintenance group, 48% (36-60) in the rituximab induction group, and 34% (27-42) in the watchful waiting group had not started new treatment.

在15年时，65%（95%置信区间56-72）的利妥昔单抗维持治疗组患者，48%（36-60）的利妥昔单抗诱导治疗组患者，以及34%（27-42）的观察等待组患者尚未开始新的治疗。

Median TTNT was not yet reached (95% CI 15·6-not estimable) in the rituximab maintenance group, 14·8 years (7·5-not reached) in the rituximab induction group, and 5·6 years (3·8-8·4) in the watchful waiting group.

中位无新治疗时间（TTNT）在利妥昔单抗维持治疗组尚未达到（95%置信区间15·6-无法估计），在利妥昔单抗诱导治疗组为14·8年（7·5-未达到），在观察等待组为5·6年（3·8-8·4）。

TTNT was longer in both the rituximab induction and rituximab maintenance groups compared with the watchful waiting group (rituximab induction vs watchful waiting: hazard ratio[HR] 0·55 [95% CI 0·38-0·80], p=0·0019; rituximab maintenance vs watchful waiting: HR 0·36 [0·26-0·50], p<0·0001).

TTNT在利妥昔单抗诱导组和利妥昔单抗维持组中均比观察等待组更长（利妥昔单抗诱导与观察等待组比较：风险比[HR] 0.55 [95% 置信区间 0.38-0.80]，p=0.0019；利妥昔单抗维持与观察等待组比较：HR 0.36 [0.26-0.50]，p<0.0001）。

interpretation

These mature data with 15 years of follow-up confirm that early rituximab monotherapy substantially delays the need for new treatment for patients with advanced stage, asymptomatic low tumour burden follicular lymphoma, providing an evidence base for its use in this setting and confirming its value for patients who seek to defer or avoid treatment with chemotherapy.

这些成熟的随访数据，随访时间为15年，证实了早期利妥昔单抗单药治疗显著推迟了对晚期、无症状、肿瘤负荷低的滤泡性淋巴瘤患者新治疗的需求，为在这一背景下使用利妥昔单抗提供了证据基础，并确认了对于那些希望推迟或避免使用化疗的患者的价值。

funding

Cancer Research UK, Lymphoma Research Trust, Lymphoma Association, and Roche.

癌症研究英国、淋巴瘤研究信托、淋巴瘤协会和罗氏公司。