Bahlis N J, Corso A, Mugge L-O, Shen Z-X, Desjardins P, Stoppa A-M, Decaux O, de Revel T, Granell M, Marit G, Nahi H, Demuynck H, Huang S-Y, Basu S, Guthrie T H, Ervin-Haynes A, Marek J, Chen G, Facon T
Tom Baker Cancer Center-University of Calgary, Calgary, Alberta, Canada.
Policlinico San Matteo Universita Di Pavia, Pavia, Italy.
Leukemia. 2017 Nov;31(11):2435-2442. doi: 10.1038/leu.2017.111. Epub 2017 Apr 4.
The phase 3, randomized Frontline Investigation of Revlimid and Dexamethasone Versus Standard Thalidomide (FIRST) trial investigating lenalidomide plus low-dose dexamethasone until disease progression (Rd continuous) vs melphalan, prednisone and thalidomide for 12 cycles (MPT) and Rd for 18 cycles (Rd18) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) showed that Rd continuous prolonged progression-free survival and overall survival compared with MPT. A subanalysis of the FIRST trial was conducted to determine the benefits of Rd continuous in patients with NDMM based on depth of response. Patients randomized 1:1:1 to Rd continuous, Rd18 or MPT were divided into subgroups based on best response: complete response (CR; n=290), ⩾very good partial response (VGPR; n=679), ⩾partial response (PR; n=1 225) or ⩽stable disease (n=299). Over 13% of patients receiving Rd continuous who achieved ⩾VGPR as best response did so beyond 18 months of treatment. Rd continuous reduced the risk of progression or death by 67%, 51% and 35% vs MPT in patients with CR, ⩾VGPR and ⩾PR, respectively. Similarly, Rd continuous reduced the risk of progression or death by 61%, 54% and 38% vs Rd18 in patients with CR, ⩾VGPR and ⩾PR, respectively. In patients with CR, ⩾VGPR or ⩾PR, 4-year survival rates in the Rd continuous arm (81.1%, 73.1% or 64.6%, respectively) were higher vs MPT (70.8%, 59.8% or 57.2%, respectively) and similar vs Rd18 (76.5%, 67.7% and 62.5%, respectively). Rd continuous improved efficacy outcomes in all responding patients, including those with CR, compared with fixed duration treatment.
一项3期随机试验——来那度胺与地塞米松对比标准沙利度胺一线研究（FIRST），在不符合移植条件的新诊断多发性骨髓瘤（NDMM）患者中，研究来那度胺加小剂量地塞米松直至疾病进展（Rd持续治疗）与美法仑、泼尼松和沙利度胺治疗12个周期（MPT）以及来那度胺加地塞米松治疗18个周期（Rd18）的疗效。结果显示，与MPT相比，Rd持续治疗可延长无进展生存期和总生存期。对FIRST试验进行了一项亚分析，以根据缓解深度确定Rd持续治疗对NDMM患者的益处。按1:1:1随机分配至Rd持续治疗组、Rd18组或MPT组的患者，根据最佳缓解情况分为亚组：完全缓解（CR；n = 290）、≥非常好的部分缓解（VGPR；n = 679）、≥部分缓解（PR；n = 1225）或≤疾病稳定（n = 299）。在接受Rd持续治疗且最佳缓解为≥VGPR的患者中，超过13%在治疗18个月后达到该缓解。与MPT相比，在CR、≥VGPR和≥PR的患者中，Rd持续治疗分别将疾病进展或死亡风险降低了67%、51%和35%。同样，与Rd18相比，在CR、≥VGPR和≥PR的患者中，Rd持续治疗分别将疾病进展或死亡风险降低了61%、54%和38%。在CR、≥VGPR或≥PR的患者中，Rd持续治疗组的4年生存率（分别为81.1%、73.1%或64.6%）高于MPT组（分别为70.8%、59.8%或57.2%），与Rd18组相似（分别为76.5%、67.7%和62.5%）。与固定疗程治疗相比，Rd持续治疗改善了所有有反应患者的疗效结果，包括CR患者。
