利妥昔单抗维持治疗对利妥昔单抗联合化疗后高肿瘤负荷滤泡性淋巴瘤患者的影响（PRIMA）：一项 3 期随机对照试验。
Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial.
机构信息
Hospices Civils de Lyon, Université Claude Bernard, UMR CNRS5239, Pierre-Bénite, France.
出版信息
Lancet. 2011 Jan 1;377(9759):42-51. doi: 10.1016/S0140-6736(10)62175-7. Epub 2010 Dec 20.
BACKGROUND
Patients with follicular lymphoma can have long survival times, but disease progression typically occurs 3-5 years after initial treatment. We assessed the potential benefit of 2 years of rituximab maintenance after first-line treatment in patients with follicular lymphoma receiving a rituximab plus chemotherapy regimen.
METHODS
The randomised, open-label PRIMA study was undertaken in 223 centres in 25 countries. 1217 patients with previously untreated follicular lymphoma needing systemic therapy received one of three non-randomised immunochemotherapy induction regimens used in routine practice. 1019 patients achieving a complete or partial response were then randomly assigned to receive 2 years of rituximab maintenance therapy (375 mg/m(2) every 8 weeks) or observation. Treatment was assigned equally by centralised block randomisation, stratified by induction regimen, response, region, and centre. Neither the participants nor those giving the interventions, assessing outcomes, and analysing data were masked to group assignments. The primary endpoint was progression-free survival (PFS). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00140582.
FINDINGS
505 patients were assigned to rituximab maintenance and 513 to observation (one patient died during randomisation). With a median follow-up of 36 months (IQR 30-42), PFS was 74·9% (95% CI 70·9-78·9) in the rituximab maintenance group (130 patients progressed) and 57·6% (53·2-62·0) in the observation group (218 progressed; hazard ratio [HR] 0·55, 95% CI 0·44-0·68, p<0·0001). 2 years after randomisation, 361 patients (71·5%) in the rituximab maintenance group were in complete or unconfirmed complete response versus 268 (52·2%) in the observation group (p=0·0001). Overall survival did not differ significantly between groups (HR 0·87, 95% CI 0·51-1·47). Grade 3 and 4 adverse events were recorded in 121 patients (24%) in the rituximab maintenance group and 84 (17%) in the observation group (risk ratio 1·46, 95% CI 1·14-1·87; p=0·0026). Infections (grades 2-4) were the most common adverse event, occurring in 197 (39%) and 123 (24%) patients, respectively (risk ratio 1·62, 95% CI 1·35-1·96; p<0·0001).
INTERPRETATION
2 years of rituximab maintenance therapy after immunochemotherapy as first-line treatment for follicular lymphoma significantly improves PFS.
FUNDING
Groupe d'Etude des Lymphomes de l'Adulte (GELA) and F Hoffmann-La Roche.
背景
滤泡性淋巴瘤患者的生存时间可能较长，但疾病通常在初始治疗后 3-5 年内进展。我们评估了在接受利妥昔单抗联合化疗方案治疗的滤泡性淋巴瘤患者中，一线治疗后进行 2 年利妥昔单抗维持治疗的潜在益处。
方法
这项随机、开放标签的 PRIMA 研究在 25 个国家的 223 个中心进行。1217 名以前未经治疗、需要全身治疗的滤泡性淋巴瘤患者接受了三种非随机免疫化疗诱导方案中的一种，这些方案在常规实践中使用。1019 名获得完全或部分缓解的患者随后被随机分配接受 2 年利妥昔单抗维持治疗（每 8 周 375mg/m2）或观察。治疗通过中央随机分组均等分配，按诱导方案、反应、区域和中心分层。参与者、给予干预措施的人员、评估结局的人员和分析数据的人员均未对分组分配进行盲法。主要终点是无进展生存期（PFS）。分析采用意向治疗。该试验在 ClinicalTrials.gov 注册，编号为 NCT00140582。
结果
505 名患者被分配至利妥昔单抗维持组，513 名患者被分配至观察组（一名患者在随机分组时死亡）。中位随访 36 个月（IQR 30-42），利妥昔单抗维持组的 PFS 为 74.9%（95%CI 70.9-78.9）（130 名患者进展），观察组为 57.6%（53.2-62.0）（218 名患者进展；风险比 [HR] 0.55，95%CI 0.44-0.68，p<0.0001）。随机分组后 2 年，利妥昔单抗维持组 361 名患者（71.5%）处于完全或未确认的完全缓解，观察组 268 名患者（52.2%）（p=0.0001）。两组的总生存期无显著差异（HR 0.87，95%CI 0.51-1.47）。利妥昔单抗维持组 121 名患者（24%）和观察组 84 名患者（17%）发生 3 级和 4 级不良事件（风险比 1.46，95%CI 1.14-1.87；p=0.0026）。感染（2-4 级）是最常见的不良事件，分别发生在 197 名（39%）和 123 名（24%）患者中（风险比 1.62，95%CI 1.35-1.96；p<0.0001）。
结论
滤泡性淋巴瘤患者一线治疗后接受 2 年利妥昔单抗维持治疗可显著改善 PFS。
资金来源
Groupe d'Etude des Lymphomes de l'Adulte（GELA）和 F Hoffmann-La Roche。
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