Rituximab after Autologous Stem-Cell Transplantation in Mantle-Cell Lymphoma
Rituximab after Autologous Stem-Cell Transplantation in Mantle-Cell Lymphoma
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DOI：
10.1056/nejmoa1701769
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发表时间：
2017-09-28
影响因子：
158.5
通讯作者：
Hermine, O.
中科院分区：
文献类型：
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作者：
Le Gouill, S.;Thieblemont, C.;Hermine, O.
背景：涎腺细胞淋巴瘤通常是不治之症。尽管在最初的免疫化疗和随后的自体干细胞移植后，完全应答率很高，但患者仍有复发。我们调查了移植后每平方米每平方米375毫克的利妥昔单抗维持治疗是否会延长反应持续时间。方法在一项涉及299名确诊时年龄在66岁以下的患者的3期试验中，我们随机分配240名患者接受利妥昔单抗维持治疗或接受自体干细胞移植后的观察(每组120名患者)；59名患者未进行随机分组。主要终点是接受随机分组的患者移植后的无事件生存(事件定义为疾病进展、复发、死亡、对利妥昔单抗过敏或严重感染)。结果经过四个疗程的免疫化疗诱导(利妥昔单抗、地塞米松、阿糖胞苷和一种铂衍生物[R-DHAP])，总有效率为89%，完全有效率为77%。257例患者进行了移植。移植后随机化的中位随访期为50.2个月(46.4~54.2个月)。从随机分组开始，利妥昔单抗组4年无事件生存率为79%(95%可信区间，70~86)，观察组为61%(95%可信区间，51~70)(P=0.001)。4年无进展生存率在利妥昔单抗组为83%(95%CI，73~88)，而观察组为%(95%CI，55~73)(P<；0.001)。利妥昔单抗组总生存率为89%(95%CI，81~94)，观察组为80%(95%CI，72~88)(P=0.04)。COX回归非校正分析显示，美罗华治疗组4年总生存率高于观察组(死亡风险比0.50；95%可信区间0.26~0.99；P=0.04)。结论移植后维持性治疗延长了年龄在66岁以下的多细胞淋巴瘤患者的无事件生存期、无进展生存期和总生存期。
BACKGROUNDMantle-cell lymphoma is generally incurable. Despite high rates of complete response after initial immunochemotherapy followed by autologous stem-cell transplantation, patients have relapses. We investigated whether rituximab maintenance therapy at a dose of 375 mg per square meter of body-surface area administered every 2 months for 3 years after transplantation would prolong the duration of response.METHODSIn a phase 3 trial involving 299 patients who were younger than 66 years of age at diagnosis, we randomly assigned 240 patients to receive rituximab maintenance therapy or to undergo observation after autologous stem-cell transplantation (120 patients per group); 59 patients did not undergo randomization. The primary end point was event-free survival (with an event defined as disease progression, relapse, death, allergy to rituximab, or severe infection) after transplantation among patients who underwent randomization.RESULTSAfter four courses of immunochemotherapy induction (rituximab, dexamethasone, cytarabine, and a platinum derivative [R-DHAP]), the overall response rate was 89%, and the complete response rate 77%. Transplantation was performed in 257 patients. The median follow-up from randomization after transplantation was 50.2 months (range, 46.4 to 54.2). Starting from randomization, the rate of event-free survival at 4 years was 79% (95% confidence interval [CI], 70 to 86) in the rituximab group versus 61% (95% CI, 51 to 70) in the observation group (P = 0.001). The rate of progression-free survival at 4 years was 83% (95% CI, 73 to 88) in the rituximab group versus 64% (95% CI, 55 to 73) in the observation group (P< 0.001). The rate of overall survival was 89% (95% CI, 81 to 94) in the rituximab group versus 80% (95% CI, 72 to 88) in the observation group (P = 0.04). According to a Cox regression unadjusted analysis, the rate of overall survival at 4 years was higher in the rituximab group than in the observation group (hazard ratio for death, 0.50; 95% CI, 0.26 to 0.99; P = 0.04).CONCLUSIONSRituximab maintenance therapy after transplantation prolonged event-free survival, progression-free survival, and overall survival among patients with mantlecell lymphoma who were younger than 66 years of age at diagnosis.