Attal Michel, Lauwers-Cances Valerie, Hulin Cyrille, Leleu Xavier, Caillot Denis, Escoffre Martine, Arnulf Bertrand, Macro Margaret, Belhadj Karim, Garderet Laurent, Roussel Murielle, Payen Catherine, Mathiot Claire, Fermand Jean P, Meuleman Nathalie, Rollet Sandrine, Maglio Michelle E, Zeytoonjian Andrea A, Weller Edie A, Munshi Nikhil, Anderson Kenneth C, Richardson Paul G, Facon Thierry, Avet-Loiseau Hervé, Harousseau Jean-Luc, Moreau Philippe
From the Institut Universitaire du Cancer de Toulouse-Oncopole (M.A., M.R., C.P., S.R., H.A.-L.) and Service d'Epidémiologie, Centre Hospitalier et Universitaire de Toulouse (V.L.-C.), Toulouse, Hôpital Haut-Lévêque, Bordeaux Pessac (C.H.), Centre Hospitalier et Universitaire la Miletrie, Poitiers (X.L.), Centre Hospitalier Le Bocage, Dijon (D.C.), Centre Hospitalier et Universitaire de Rennes, Rennes (M.E.), Hôpital St.-Louis (B.A., J.P.F.), Centre Hospitalier Universitaire, Hôpital St.-Antoine (L.G.), Institut Curie (C.M.), and Haute Autorité de Santé (J.-L.H.), Paris, Institut d'Hématologie de Basse Normandie, Centre Hospitalier et Universitaire de Caen, Caen (M.M.), Centre Hospitalier et Universitaire Henri Mondor, Creteil (K.B.), Hôpital Claude Huriez, Lille (T.F.), and Hôtel Dieu, Nantes (P.M.) - all in France; Institut Jules Bordet, Brussels (N. Meuleman); and Dana-Farber Cancer Institute, Boston (M.E.M., A.A.Z., E.A.W., N. Munshi, K.C.A., P.G.R.).
N Engl J Med. 2017 Apr 6;376(14):1311-1320. doi: 10.1056/NEJMoa1611750.
High-dose chemotherapy plus autologous stem-cell transplantation has been the standard treatment for newly diagnosed multiple myeloma in adults up to 65 years of age. However, promising data on the use of combination therapy with lenalidomide, bortezomib, and dexamethasone (RVD) in this population have raised questions about the role and timing of transplantation.
We randomly assigned 700 patients with multiple myeloma to receive induction therapy with three cycles of RVD and then consolidation therapy with either five additional cycles of RVD (350 patients) or high-dose melphalan plus stem-cell transplantation followed by two additional cycles of RVD (350 patients). Patients in both groups received maintenance therapy with lenalidomide for 1 year. The primary end point was progression-free survival.
Median progression-free survival was significantly longer in the group that underwent transplantation than in the group that received RVD alone (50 months vs. 36 months; adjusted hazard ratio for disease progression or death, 0.65; P<0.001). This benefit was observed across all patient subgroups, including those stratified according to International Staging System stage and cytogenetic risk. The percentage of patients with a complete response was higher in the transplantation group than in the RVD-alone group (59% vs. 48%, P=0.03), as was the percentage of patients in whom minimal residual disease was not detected (79% vs. 65%, P<0.001). Overall survival at 4 years did not differ significantly between the transplantation group and the RVD-alone group (81% and 82%, respectively). The rate of grade 3 or 4 neutropenia was significantly higher in the transplantation group than in the RVD-alone group (92% vs. 47%), as were the rates of grade 3 or 4 gastrointestinal disorders (28% vs. 7%) and infections (20% vs. 9%). No significant between-group differences were observed in the rates of treatment-related deaths, second primary cancers, thromboembolic events, and peripheral neuropathy.
Among adults with multiple myeloma, RVD therapy plus transplantation was associated with significantly longer progression-free survival than RVD therapy alone, but overall survival did not differ significantly between the two approaches. (Supported by Celgene and others; IFM 2009 Study ClinicalTrials.gov number, NCT01191060 .).
高剂量化疗加自体干细胞移植一直是65岁及以下新诊断的成年多发性骨髓瘤患者的标准治疗方法。然而，有关来那度胺、硼替佐米和地塞米松联合治疗（RVD）在该人群中应用的有前景的数据引发了关于移植的作用和时机的问题。
我们将700例多发性骨髓瘤患者随机分配，接受三个周期RVD的诱导治疗，然后分别接受另外五个周期RVD的巩固治疗（350例患者）或大剂量美法仑加干细胞移植，随后再接受两个周期RVD的巩固治疗（350例患者）。两组患者均接受来那度胺维持治疗1年。主要终点为无进展生存期。
接受移植的组中位无进展生存期显著长于单纯接受RVD治疗的组（50个月对36个月；疾病进展或死亡的校正风险比，0.65；P<0.001）。在所有患者亚组中均观察到这一益处，包括根据国际分期系统分期和细胞遗传学风险分层的亚组。移植组完全缓解的患者百分比高于单纯RVD组（59%对48%，P=0.03），未检测到微小残留病的患者百分比也是如此（79%对65%，P<0.001）。移植组和单纯RVD组4年总生存率无显著差异（分别为81%和82%）。移植组3或4级中性粒细胞减少症的发生率显著高于单纯RVD组（92%对47%），3或4级胃肠道疾病（28%对7%）和感染（20%对9%）的发生率也是如此。在治疗相关死亡、第二原发性癌症、血栓栓塞事件和周围神经病变的发生率方面，未观察到显著的组间差异。
在成年多发性骨髓瘤患者中，RVD治疗加移植与单纯RVD治疗相比，无进展生存期显著更长，但两种治疗方法的总生存率无显著差异。（由新基公司等资助；IFM 2009研究ClinicalTrials.gov编号，NCT01191060。）
