Department of Hematology, Hôpital Purpan, Toulouse, France.
N Engl J Med. 2012 May 10;366(19):1782-91. doi: 10.1056/NEJMoa1114138.
High-dose chemotherapy with autologous stem-cell transplantation is a standard treatment for young patients with multiple myeloma. Residual disease is almost always present after transplantation and is responsible for relapse. This phase 3, placebo-controlled trial investigated the efficacy of lenalidomide maintenance therapy after transplantation.
We randomly assigned 614 patients younger than 65 years of age who had nonprogressive disease after first-line transplantation to maintenance treatment with either lenalidomide (10 mg per day for the first 3 months, increased to 15 mg if tolerated) or placebo until relapse. The primary end point was progression-free survival.
Lenalidomide maintenance therapy improved median progression-free survival (41 months, vs. 23 months with placebo; hazard ratio, 0.50; P<0.001). This benefit was observed across all patient subgroups, including those based on the β(2)-microglobulin level, cytogenetic profile, and response after transplantation. With a median follow-up period of 45 months, more than 70% of patients in both groups were alive at 4 years. The rates of grade 3 or 4 peripheral neuropathy were similar in the two groups. The incidence of second primary cancers was 3.1 per 100 patient-years in the lenalidomide group versus 1.2 per 100 patient-years in the placebo group (P=0.002). Median event-free survival (with events that included second primary cancers) was significantly improved with lenalidomide (40 months, vs. 23 months with placebo; P<0.001).
Lenalidomide maintenance after transplantation significantly prolonged progression-free and event-free survival among patients with multiple myeloma. Four years after randomization, overall survival was similar in the two study groups. (Funded by the Programme Hospitalier de Recherche Clinique and others; ClinicalTrials.gov number, NCT00430365.).
大剂量化疗联合自体造血干细胞移植是治疗年轻多发性骨髓瘤患者的标准疗法。移植后几乎总会残留疾病，这是疾病复发的原因。这项 3 期、安慰剂对照试验研究了移植后来那度胺维持治疗的疗效。
我们将 614 名年龄小于 65 岁且一线移植后疾病无进展的患者随机分配，接受来那度胺（前 3 个月每天 10 毫克，如果耐受则增加至 15 毫克）或安慰剂维持治疗，直至复发。主要终点是无进展生存。
来那度胺维持治疗改善了中位无进展生存期（41 个月 vs. 安慰剂组的 23 个月；风险比，0.50；P<0.001）。这一益处见于所有患者亚组，包括基于β(2)-微球蛋白水平、细胞遗传学特征和移植后反应的亚组。中位随访 45 个月时，两组超过 70%的患者在 4 年时仍存活。两组的 3 级或 4 级周围神经病发生率相似。来那度胺组的第二原发癌发生率为每 100 患者-年 3.1 例，安慰剂组为每 100 患者-年 1.2 例（P=0.002）。来那度胺组的中位无事件生存（包括第二原发癌的事件）显著延长（40 个月 vs. 安慰剂组的 23 个月；P<0.001）。
移植后使用来那度胺维持治疗可显著延长多发性骨髓瘤患者的无进展和无事件生存。随机分组后 4 年时，两组的总生存相似。（由 Programme Hospitalier de Recherche Clinique 等资助；ClinicalTrials.gov 注册号：NCT00430365。）
