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.).
N Engl J Med. 2018 Sep 6;379(10):934-947. doi: 10.1056/NEJMoa1805104.
Rituximab plus chemotherapy has been shown to be effective in patients with advanced-stage, previously untreated follicular lymphoma; nevertheless, most patients will have a relapse. Combination immunotherapy with lenalidomide and rituximab is an immunomodulatory regimen that has shown promising activity in patients with indolent B-cell non-Hodgkin's lymphoma.
We conducted this multicenter, international, phase 3 superiority trial to evaluate rituximab plus lenalidomide, as compared with rituximab plus chemotherapy, in patients with previously untreated follicular lymphoma. Patients were randomly assigned to receive one of the two regimens, followed by maintenance monotherapy with rituximab. Treatment with rituximab plus lenalidomide consisted of 18 cycles of the two drugs, followed by rituximab maintenance therapy every 8 weeks for 12 cycles (six additional doses). Treatment with rituximab plus chemotherapy consisted of the investigator's choice of one of three rituximab-based regimens, followed by maintenance monotherapy with rituximab every 8 weeks for 12 cycles. The primary end points were complete response (confirmed or unconfirmed) at 120 weeks and progression-free survival.
A total of 1030 patients were randomly assigned to receive rituximab plus lenalidomide (513 patients) or rituximab plus chemotherapy (517 patients). The rate of confirmed or unconfirmed complete response at 120 weeks was similar in the two groups: 48% (95% confidence interval [CI], 44 to 53) in the rituximab-lenalidomide group and 53% (95% CI, 49 to 57) in the rituximab-chemotherapy group (P=0.13). The interim 3-year rate of progression-free survival was 77% (95% CI, 72 to 80) and 78% (95% CI, 74 to 82), respectively. A higher percentage of patients in the rituximab-chemotherapy group had grade 3 or 4 neutropenia (32% vs. 50%) and febrile neutropenia of any grade (2% vs. 7%), and a higher percentage of patients in the rituximab-lenalidomide group had grade 3 or 4 cutaneous reactions (7% vs. 1%).
Among patients with previously untreated follicular lymphoma, efficacy results were similar with rituximab plus lenalidomide and rituximab plus chemotherapy (with both regimens followed by rituximab maintenance therapy). The safety profile differed in the two groups. (Funded by Celgene; RELEVANCE ClinicalTrials.gov numbers, NCT01476787 and NCT01650701 , and EudraCT number, 2011-002792-42 .).
利妥昔单抗联合化疗已被证实对未经治疗的晚期滤泡性淋巴瘤患者有效；然而，大多数患者仍会复发。来那度胺联合利妥昔单抗的联合免疫治疗是一种免疫调节方案，在惰性 B 细胞非霍奇金淋巴瘤患者中显示出了有希望的活性。
我们进行了这项多中心、国际、3 期优效性试验，以评估未经治疗的滤泡性淋巴瘤患者中利妥昔单抗联合来那度胺与利妥昔单抗联合化疗相比的效果。患者被随机分配接受两种方案中的一种，随后接受利妥昔单抗单药维持治疗。利妥昔单抗联合来那度胺的治疗方案包括两种药物的 18 个周期，随后每 8 周进行 12 个周期的利妥昔单抗维持治疗（共 6 个额外剂量）。利妥昔单抗联合化疗的治疗方案为研究者选择的三种基于利妥昔单抗的方案之一，随后每 8 周进行 12 个周期的利妥昔单抗单药维持治疗。主要终点为 120 周时的完全缓解（确认或未确认）和无进展生存期。
共有 1030 名患者被随机分配接受利妥昔单抗联合来那度胺（513 名）或利妥昔单抗联合化疗（517 名）。两组 120 周时确认或未确认的完全缓解率相似：利妥昔单抗-来那度胺组为 48%（95%置信区间[CI]，44 至 53），利妥昔单抗-化疗组为 53%（95%CI，49 至 57）（P=0.13）。中位 3 年无进展生存率分别为 77%（95%CI，72 至 80）和 78%（95%CI，74 至 82）。利妥昔单抗-化疗组中 3 级或 4 级中性粒细胞减少症（32% vs. 50%）和任何级别发热性中性粒细胞减少症（2% vs. 7%）的患者比例较高，利妥昔单抗-来那度胺组中 3 级或 4 级皮肤反应（7% vs. 1%）的患者比例较高。
在未经治疗的滤泡性淋巴瘤患者中，利妥昔单抗联合来那度胺和利妥昔单抗联合化疗的疗效结果相似（两种方案均随后进行利妥昔单抗维持治疗）。两组的安全性特征不同。（由 Celgene 资助；RELEVANCE ClinicalTrials.gov 编号，NCT01476787 和 NCT01650701，和 EudraCT 编号，2011-002792-42。）
