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利妥昔单抗联合来那度胺治疗未接受过治疗的晚期滤泡性淋巴瘤
Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma


Franck Morschhauser ... 肿瘤 • 2018.09.06
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摘要


背景

利妥昔单抗+化疗已被证明对既往未接受过治疗的晚期滤泡性淋巴瘤患者有效;然而,大多数患者会复发。利妥昔单抗+来那度胺联合免疫疗法是一种免疫调节治疗方案,该方案在惰性B细胞非霍奇金淋巴瘤患者中显示出有希望的活性。

 

方法

我们开展了这项多中心、国际性、3期优效性试验,在既往未接受过治疗的滤泡性淋巴瘤患者中,评估利妥昔单抗+来那度胺,并与利妥昔单抗+化疗进行比较。患者被随机分组,接受以下两种方案之一,随后接受维持性利妥昔单抗单独治疗。利妥昔单抗+来那度胺方案包括两种药物治疗18个周期,随后每8周1次利妥昔单抗维持治疗12个周期(额外6剂)。利妥昔单抗+化疗方案包括研究者选择的三种基于利妥昔单抗的方案之一,随后每8周1次维持性利妥昔单抗单独治疗12个周期。主要终点为120周时完全缓解(已确认或未确认)和无进展生存。

 

结果

共有1,030例患者被随机分组,接受利妥昔单抗+来那度胺(513例患者)或利妥昔单抗+化疗(517例患者)治疗。在两组中,120周时已确认或未确认的完全缓解的发生率相似:利妥昔单抗+来那度胺组48%(95%置信区间[CI],44%~53%)和利妥昔单抗+化疗组53%(95% CI,49%~57%)(P=0.13)。期中3年无进展生存率分别为77%(95% CI,72%~80%)和78%(95% CI,74%~82%)。利妥昔单抗+化疗组出现3级或4级中性粒细胞减少(32% vs. 50%)和任何级别的发热性中性粒细胞减少(2% vs. 7%)的患者百分比较高,利妥昔单抗+来那度胺组出现3级或4级皮肤反应的患者百分比较高(7% vs. 1%)。

 

结论

在既往未接受过治疗的滤泡性淋巴瘤患者中,利妥昔单抗+来那度胺和利妥昔单抗+化疗的疗效结果相似(两种方案治疗后均进行了利妥昔单抗维持治疗)。两组的安全性不同(由新基医药[Celgene]资助;RELEVANCE在ClinicalTrials.gov注册号为NCT01476787和NCT01650701,在EudraCT注册号为2011-002792-42)。





作者信息

Franck Morschhauser, M.D., Ph.D., Nathan H. Fowler, M.D., Pierre Feugier, M.D., Reda Bouabdallah, M.D., Hervé Tilly, M.D., M. Lia Palomba, M.D., Christophe Fruchart, M.D., Edward N. Libby, M.D., Rene-Olivier Casasnovas, M.D., Ian W. Flinn, M.D., Ph.D., Corinne Haioun, M.D., Hervé Maisonneuve, M.D., Loic Ysebaert, M.D., Nancy L. Bartlett, M.D., Kamal Bouabdallah, M.D., Pauline Brice, M.D., Vincent Ribrag, M.D., Nicolas Daguindau, M.D., Steven Le Gouill, M.D., Gian M. Pica, M.D., Alejandro Martin Garcia-Sancho, M.D., Ph.D., Armando López-Guillermo, M.D., Jean-François Larouche, M.D., Kiyoshi Ando, M.D., Ph.D., Maria Gomes da Silva, M.D., Ph.D., Marc André, M.D., Pierre Zachée, M.D., Laurie H. Sehn, M.D., Kensei Tobinai, M.D., Guillaume Cartron, M.D., Ph.D., David Liu, M.D., Ph.D., Jianming Wang, Ph.D., Luc Xerri, M.D., Ph.D., and Gilles A. Salles, M.D., Ph.D. for the RELEVANCE Trial Investigators*
From Université Lille, Centre Hospitalier Universitaire (CHU), Groupe de Recherche sur les formes Injectables et les Technologies Associées, Lille (F.M.), CHU Régional de Nancy, Service d’Hématologie, Vandoeuvre lès Nancy (P.F.), Institut Paoli-Calmettes (R.B.) and Department of Pathology, Institut Paoli-Calmettes, Centre de Recherche en Cancerologie de Marseille, INSERM, Centre National de la Recherche Scientifique, Aix-Marseille Université (L.X.), Marseille, Centre Henri Becquerel, Unité 1245 and Département d’Hématologie, Université de Rouen, Rouen (H.T.), Institut d’Hématologie de Basse Normandie, Caen (C.F.), CHU Le Bocage Service d’Hématologie Clinique, Dijon (R.-O.C.), Hôpital Henri Mondor Unité Hémopathies Lymphoïdes, Créteil (C.H.), Centre Hospitalier Départemental Vendée Service d’Onco-Hématologie, La Roche sur Yon (H.M.), Institut Universitaire du Cancer de Toulouse Oncopole Service d’Hématologie, Toulouse (L.Y.), CHU Bordeaux, Service d’Hématologie, Bordeaux (K.B.), Hôpital Saint Louis Service d’Onco-Hématologie, Paris (P.B.), Gustave Roussy Cancer, Villejuif (V.R.), Centre Hospitalier Annecy Genevois Service, Annecy (N.D.), CHU de Nantes–Hôtel Dieu Service d’Hématologie Clinique, Centre de Recherche en Cancerologie et Immunologie, INSERM, Centre National de la Recherche Scientifique, Université de Nantes, Nantes (S.L.G.), Centre Hospitalier Métropole Savoie Service Hématologie, Chambery (G.M.P.), Department of Hematology, CHU Montpellier, University of Montpellier, Montpellier (G.C.), and Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, University of Lyon, Pierre-Benite (G.A.S.) — all in France; the Department of Lymphoma and Myeloma, University of Texas M.D. Anderson Cancer Center, Houston (N.H.F.); the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (M.L.P.); the Department of Medicine, Division of Medical Oncology, University of Washington, Seattle (E.N.L.); Sarah Cannon Research Institute–Tennessee Oncology, Nashville (I.W.F.); Washington University School of Medicine, Siteman Cancer Center, St. Louis (N.L.B.); the Department of Hematology, Hospital Universitario de Salamanca and Instituto de Investigación Biomédica de Salamanca, Centro de Investigación Biomédica en Red de Cáncer, Salamanca (A.M.G.-S.), and the Department of Hematology, Hospital Clinic de Barcelona, Barcelona (A.L.-G.) — both in Spain; CHU de Québec, Hôpital de l’Enfant-Jésus, Quebec (J.-F.L.), and British Columbia Cancer Centre for Lymphoid Cancer, University of British Columbia, Vancouver (L.H.S.) — both in Canada; the Department of Hematology and Oncology, Tokai University Hospital, Kanagawa, Japan (K.A.); Instituto Português de Oncologia Lisboa Francisco Gentil Departamento de Hematologia, Lisbon (M.G.S.); the Department of Hematology, CHU Université Catholique de Louvain Namur, Yvoir (M.A.), and the Department of Hematology, Ziekenhuis Netwerk Antwerpen Stuivenberg, Antwerp (P.Z.) — both in Belgium; the Department of Hematology, National Cancer Center Hospital, Tokyo, Japan (K.T.); and Celgene, Summit, NJ (D.L., J.W.). Address reprint requests to Dr. Morschhauser at the University of Lille, CHU Lille, EA 7365, GRITA– Groupe de Recherche sur les formes Injectables et les Technologies Associées, F-59000 Lille, France, or at franck.morschhauser@chru-lille.fr. *A complete list of investigators in the RELEVANCE trial is provided in the Supplementary Appendix, available at NEJM.org.

 

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