Lenalidomide after stem-cell transplantation for multiple myeloma.
Lenalidomide after stem-cell transplantation for multiple myeloma.
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DOI：
10.1056/nejmoa1114083
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发表时间：
2012-05-10
期刊：
影响因子：
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通讯作者：
Linker C
中科院分区：
文献类型：
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作者：
McCarthy PL;Owzar K;Hofmeister CC;Hurd DD;Hassoun H;Richardson PG;Giralt S;Stadtmauer EA;Weisdorf DJ;Vij R;Moreb JS;Callander NS;Van Besien K;Gentile T;Isola L;Maziarz RT;Gabriel DA;Bashey A;Landau H;Martin T;Qazilbash MH;Levitan D;McClune B;Schlossman R;Hars V;Postiglione J;Jiang C;Bennett E;Barry S;Bressler L;Kelly M;Seiler M;Rosenbaum C;Hari P;Pasquini MC;Horowitz MM;Shea TC;Devine SM;Anderson KC;Linker C
目前尚缺乏关于来那度胺维持治疗是否延长多发性骨髓瘤患者自体造血干细胞移植后疾病进展时间的数据。在2005年4月至2009年7月期间，我们将460例年龄小于71岁且在干细胞移植后100天病情稳定或边缘、部分或完全缓解的患者随机分配至来那度胺或安慰剂组，直至疾病进展。来那度胺的起始剂量为10 mg/天（范围，5 - 15）。研究药物分配在2009年揭盲，当时计划的中期分析显示来那度胺组的疾病进展时间显著延长。在揭盲时，20%接受来那度胺治疗的患者和44%接受安慰剂治疗的患者出现疾病进展或死亡（P<0.001）;在其余128例接受安慰剂治疗且未出现疾病进展的患者中，86例交叉至来那度胺治疗。在中位随访34个月时，231例接受来那度胺治疗的患者中有86例（37%）和229例接受安慰剂治疗的患者中有132例（58%）出现疾病进展或死亡。来那度胺组的中位进展时间为46个月，安慰剂组为27个月（P<0.001）。共有35名接受来那度胺治疗的患者（15%）和53名接受安慰剂治疗的患者（23%）死亡（P=0.03）。接受来那度胺治疗的患者发生更多的3级或4级血液学不良事件和3级非血液学不良事件（两项比较P<0.001）。第二原发性癌症发生在18例接受来那度胺的患者（8%）和6例接受安慰剂的患者（3%）中。在骨髓瘤患者中，造血干细胞移植后第100天开始的来那度胺维持治疗与更多的毒性和继发性癌症相关，但疾病进展时间显著延长，总生存率显著提高。（由国家癌症研究所资助; ClinicalTrials.gov编号，NCT 00114101。
Data are lacking on whether lenalidomide maintenance therapy prolongs the time to disease progression after autologous hematopoietic stem-cell transplantation in patients with multiple myeloma. Between April 2005 and July 2009, we randomly assigned 460 patients who were younger than 71 years of age and had stable disease or a marginal, partial, or complete response 100 days after undergoing stem-cell transplantation to lenalidomide or placebo, which was administered until disease progression. The starting dose of lenalidomide was 10 mg per day (range, 5 to 15). The study-drug assignments were unblinded in 2009, when a planned interim analysis showed a significantly longer time to disease progression in the lenalidomide group. At unblinding, 20% of patients who received lenalidomide and 44% of patients who received placebo had progressive disease or had died (P<0.001); of the remaining 128 patients who received placebo and who did not have progressive disease, 86 crossed over to lenalidomide. At a median follow-up of 34 months, 86 of 231 patients who received lenalidomide (37%) and 132 of 229 patients who received placebo (58%) had disease progression or had died. The median time to progression was 46 months in the lenalidomide group and 27 months in the placebo group (P<0.001). A total of 35 patients who received lenalidomide (15%) and 53 patients who received placebo (23%) died (P=0.03). More grade 3 or 4 hematologic adverse events and grade 3 non-hematologic adverse events occurred in patients who received lenalidomide (P<0.001 for both comparisons). Second primary cancers occurred in 18 patients who received lenalidomide (8%) and 6 patients who received placebo (3%). Lenalidomide maintenance therapy, initiated at day 100 after hematopoietic stem-cell transplantation, was associated with more toxicity and second cancers but a significantly longer time to disease progression and significantly improved overall survival among patients with myeloma. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00114101.)