摘要
背景
对于新近确诊的65岁以下多发性骨髓瘤成人患者，大剂量化疗联合自体干细胞移植一直是标准治疗方案。来那度胺、硼替佐米和地塞米松联合治疗方案（RVD）在该患者群体中获得了令人鼓舞的结果；然而，这些结果引出了关于移植所起的作用和时机的问题。
方法
我们将700例多发性骨髓瘤患者随机分组，所有患者均先接受3个周期RVD诱导治疗；之后，一组再接受5个周期RVD巩固治疗（350例），另一组接受大剂量美法仑联合干细胞移植，继之以2个周期的RVD治疗（350例）。2组患者均接受来那度胺维持治疗1年。主要终点是无进展生存期。
结果
与RVD单独治疗组的患者相比，移植组的中位无进展生存期显著延长（50个月对36个月；调整后的疾病进展或死亡的风险比为0.65；P＜0.001）。我们在所有患者亚组均观察到该治疗获益，包括根据不同分期（依据国际分期系统[International Staging System]确定）和细胞遗传学危险度进行分层的患者。移植组中获得完全缓解的患者百分比高于RVD单独治疗组（59%对48%，P=0.03），微小残留病未检出的患者百分比也是如此（79%对65%，P＜0.001）。在第4年时，移植组和RVD单独治疗组的总生存率没有显著差异（分别为81%和82%）。与RVD单独治疗组相比，移植组中下列不良事件的发生率显著高于RVD单独治疗组：3级或4级中性粒细胞减少（92%对47%），3级或4级胃肠道疾病（28%对7%）和感染（20%对9%）。对于下列事件的发生率，我们未观察到两组间有显著差异：治疗相关死亡、第二原发癌、血栓栓塞事件和周围神经病变。
结论
在多发性骨髓瘤成人患者中，与RVD单独治疗相比，RVD治疗联合移植可显著延长无进展生存期，但两种治疗方法的总生存期没有显著差异（由新基[Celgene]公司等资助；IFM 2009研究在ClinicalTrials.gov注册号为NCT01191060）。
作者信息
Michel Attal, M.D., Valerie Lauwers-Cances, M.D., Cyrille Hulin, M.D., Xavier Leleu, M.D., Denis Caillot, M.D., Martine Escoffre, M.D., Bertrand Arnulf, M.D., Margaret Macro, M.D., Karim Belhadj, M.D., Laurent Garderet, M.D., Murielle Roussel, M.D., Catherine Payen, M.D., Claire Mathiot, M.D., Jean P. Fermand, M.D., Nathalie Meuleman, M.D., Sandrine Rollet, M.S., Michelle E. Maglio, B.S., Andrea A. Zeytoonjian, B.S., Edie A. Weller, Ph.D., Nikhil Munshi, M.D., Kenneth C. Anderson, M.D., Paul G. Richardson, M.D., Thierry Facon, M.D., Hervé Avet-Loiseau, M.D., Jean-Luc Harousseau, M.D., and Philippe Moreau, M.D., for the IFM 2009 Study*
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.). Address reprint requests to Dr. Attal at the Institut Universitaire du Cancer de Toulouse-Oncopole, 1 Ave. Irène Joliot Curie, 31059 Toulouse, France, or at attal.michel@iuct-oncopole.fr.
*A complete list of investigators in the Intergroupe Francophone du Myélome (IFM) 2009 Study is provided in the Supplementary Appendix, available at NEJM.org.
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