Department of Hematology, Charles University Hospital, Prague, Czech Republic.
Department of Hematology, Rennes University Hospital, Rennes, France.
Lancet Oncol. 2016 Mar;17(3):319-331. doi: 10.1016/S1470-2045(15)00559-8. Epub 2016 Feb 16.
Lenalidomide, an immunomodulatory drug with antineoplastic and antiproliferative effects, showed activity in many single-group studies in relapsed or refractory mantle cell lymphoma. The aim of this randomised study was to examine the efficacy and safety of lenalidomide versus best investigator's choice of single-agent therapy in relapsed or refractory mantle cell lymphoma.
The MCL-002 (SPRINT) study was a randomised, phase 2 study of patients with mantle cell lymphoma aged 18 years or older at 67 clinics and academic centres in 12 countries who relapsed one to three times, had Eastern Cooperative Oncology Group performance status of 0-2, at least one measurable lesion to be eligible, and who were ineligible for intensive chemotherpy or stem-cell transplantation. Using a centralised interactive voice response system, we randomly assigned (2:1) patients in a permuted block size of six to receive lenalidomide (25 mg orally on days 1-21 every 28 days) until progressive disease or intolerability, or single-agent investigator's choice of either rituximab, gemcitabine, fludarabine, chlorambucil, or cytarabine. Randomisation was stratified by time from diagnosis, time from last anti-lymphoma therapy, and previous stem-cell transplantation. Individual treatment assignment between lenalidomide and investigator's choice was open label, but investigators had to register their choice of comparator drug before randomly assigning a patient. Patients who progressed on investigator's choice could cross over to lenalidomide treatment. We present the prespecified primary analysis results in the intention-to-treat population for the primary endpoint of progression-free survival, defined as the time from randomisation to progressive disease or death, whichever occurred first. Patient enrolment is complete, although treatment and collection of additional time-to-event data are ongoing. This study is registered with ClinicalTrials.gov, number NCT00875667.
Between April 30, 2009, and March 7, 2013, we enrolled 254 patients in the intention-to-treat population (170 [67%] were randomly assigned to receive lenalidomide, 84 [33%] to receive investigator's choice monotherapy). Patients had a median age of 68·5 years and received a median of two previous regimens. With a median follow-up of 15·9 months (IQR 7·6-31·7), lenalidomide significantly improved progression-free survival compared with investigator's choice (median 8·7 months [95% CI 5·5-12·1] vs 5·2 months [95% CI 3·7-6·9]) with a hazard ratio of 0·61 (95% CI 0·44-0·84; p=0·004). In the 167 patients in the lenalidomide group and 83 patients in the investigator's choice group who received at least one dose of treatment the most common grade 3-4 adverse events included neutropenia (73 [44%] of 167 vs 28 [34%] of 83) without increased risk of infection, thrombocytopenia (30 [18%] vs 23 [28%]), leucopenia (13 [8%] vs nine [11%]), and anaemia (14 [8%] vs six [7%]).
Patients with relapsed or refractory mantle cell lymphoma ineligible for intensive chemotherapy or stem-cell transplantation have longer progression-free survival, with a manageable safety profile when treated with lenalidomide compared with monotherapy investigator's choice options.
Celgene Corporation.
来那度胺是一种具有免疫调节作用的抗肿瘤和抗增殖药物，在许多复发或难治性套细胞淋巴瘤的单组研究中显示出活性。本随机研究的目的是检查来那度胺与复发或难治性套细胞淋巴瘤中研究者选择的单药治疗相比的疗效和安全性。
MCL-002（SPRINT）研究是一项在 12 个国家的 67 个诊所和学术中心进行的随机、2 期研究，纳入了年龄在 18 岁及以上的复发 1 至 3 次、东部合作肿瘤组（ECOG）表现状态为 0-2、至少有一个可测量的病变符合条件且不适合强化化疗或干细胞移植的套细胞淋巴瘤患者。使用集中式交互式语音应答系统，我们按照 6 的置换块大小（2:1）随机分配患者接受来那度胺（25mg 口服，第 1-21 天，每 28 天一次），直到疾病进展或不耐受，或研究者选择的单药利妥昔单抗、吉西他滨、氟达拉滨、苯丁酸氮芥或阿糖胞苷。分层因素为从诊断到上次抗淋巴瘤治疗的时间和以前的干细胞移植。来那度胺和研究者选择之间的个体治疗分配是开放标签的，但在随机分配患者之前，研究者必须登记他们选择的比较药物。接受研究者选择治疗后进展的患者可以交叉到来那度胺治疗。我们报告了意向治疗人群中无进展生存的主要终点的预先指定的主要分析结果，无进展生存定义为从随机分组到疾病进展或死亡的时间，以先发生者为准。尽管正在进行治疗和收集额外的时间至事件数据，但患者的招募已经完成。这项研究在 ClinicalTrials.gov 注册，编号为 NCT00875667。
2009 年 4 月 30 日至 2013 年 3 月 7 日，我们在意向治疗人群中招募了 254 名患者（170 名[67%]随机分配接受来那度胺，84 名[33%]接受研究者选择的单药治疗）。患者的中位年龄为 68.5 岁，中位接受了两次以前的治疗方案。中位随访时间为 15.9 个月（IQR 7.6-31.7），与研究者选择相比，来那度胺显著改善了无进展生存（中位 8.7 个月[95%CI 5.5-12.1] vs 5.2 个月[95%CI 3.7-6.9]），风险比为 0.61（95%CI 0.44-0.84；p=0.004）。在接受至少一剂治疗的 167 名来那度胺组患者和 83 名研究者选择组患者中，最常见的 3-4 级不良事件包括中性粒细胞减少症（73[44%]vs 28[34%]），无感染风险增加，血小板减少症（30[18%]vs 23[28%]），白细胞减少症（13[8%]vs 9[11%]）和贫血症（14[8%]vs 6[7%]）。
不适合强化化疗或干细胞移植的复发或难治性套细胞淋巴瘤患者，与研究者选择的单药治疗相比，接受来那度胺治疗时无进展生存期更长，安全性可管理。
Celgene Corporation。
