From Winship Cancer Institute, Emory University School of Medicine, Atlanta (S.L.); National and Kapodistrian University of Athens, Athens (M.D.); A.O.U. San Giovanni Battista di Torino-Ospedale Molinette, Turin, Italy (A.P.); QEII Health Science Center and Dalhousie University, Halifax, NS (D.W.), Cross Cancer Institute and University of Alberta, Edmonton (A.B.), and Princess Margaret Cancer Centre, Toronto (D.R.) - all in Canada; Silesian Medical University, Katowice (S.G.), and Medical University of Lublin, Lublin (A.W.-C.) - both in Poland; Charles University Hospital, Prague, Czech Republic (I.S.); University Hospital, Nantes, France (P.M.); Complejo Asistencial Universitario de Salamanca-Instituto de Investigación Biomédica de Salamanca, Salamanca (M.-V.M.), and Clinica Universidad de Navarra-Centro de Investigación Médica Aplicada, Instituto de Investigación Sanitaria de Navarra, Pamplona (J.S.-M.) - both in Spain; Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, and Tel Aviv University, Ramat Aviv - both in Israel (H.M.); Ankara University, Ankara, Turkey (M.B.); Alfred Health-Monash University, Melbourne, VIC, Australia (A. Spencer); Barts and the London NHS Trust, London (H.O.); University of Texas M.D. Anderson Cancer Center, Houston (R.Z.O.); Kyoto Prefectural University of Medicine, Kyoto (M.T.), and Nishigunma National Hospital, Shibukawa (M.M.) - both in Japan; Universitätsklinikum der Technische Universität, Dresden (C.R.), and Universitätsklinikum Würzburg, Würzburg (H.E.) - both in Germany; Zeikenhuis Netwerk Antwerpen (ZNA) Stuivenberg, Antwerp, Belgium (K.L.W.); AbbVie Biotherapeutics, Redwood City, CA (A. Singhal); Bristol-Myers Squibb, Princeton, NJ (J.K.), Wallingford, CT (E.B.), and Braine-l'Alleud, Belgium (V.P.); and Dana-Farber Cancer Institute, Boston (K.C.A., P.R.).
N Engl J Med. 2015 Aug 13;373(7):621-31. doi: 10.1056/NEJMoa1505654. Epub 2015 Jun 2.
BACKGROUND: Elotuzumab, an immunostimulatory monoclonal antibody targeting signaling lymphocytic activation molecule F7 (SLAMF7), showed activity in combination with lenalidomide and dexamethasone in a phase 1b-2 study in patients with relapsed or refractory multiple myeloma. METHODS: In this phase 3 study, we randomly assigned patients to receive either elotuzumab plus lenalidomide and dexamethasone (elotuzumab group) or lenalidomide and dexamethasone alone (control group). Coprimary end points were progression-free survival and the overall response rate. Final results for the coprimary end points are reported on the basis of a planned interim analysis of progression-free survival. RESULTS: Overall, 321 patients were assigned to the elotuzumab group and 325 to the control group. After a median follow-up of 24.5 months, the rate of progression-free survival at 1 year in the elotuzumab group was 68%, as compared with 57% in the control group; at 2 years, the rates were 41% and 27%, respectively. Median progression-free survival in the elotuzumab group was 19.4 months, versus 14.9 months in the control group (hazard ratio for progression or death in the elotuzumab group, 0.70; 95% confidence interval, 0.57 to 0.85; P<0.001). The overall response rate in the elotuzumab group was 79%, versus 66% in the control group (P<0.001). Common grade 3 or 4 adverse events in the two groups were lymphocytopenia, neutropenia, fatigue, and pneumonia. Infusion reactions occurred in 33 patients (10%) in the elotuzumab group and were grade 1 or 2 in 29 patients. CONCLUSIONS: Patients with relapsed or refractory multiple myeloma who received a combination of elotuzumab, lenalidomide, and dexamethasone had a significant relative reduction of 30% in the risk of disease progression or death. (Funded by Bristol-Myers Squibb and AbbVie Biotherapeutics; ELOQUENT-2 ClinicalTrials.gov number, NCT01239797.).
背景：靶向信号淋巴细胞激活分子 F7（SLAMF7）的免疫刺激单克隆抗体依鲁替尼（elotuzumab）在复发或难治性多发性骨髓瘤患者中进行的 1b-2 期研究中，与来那度胺和地塞米松联合显示出疗效。
方法：在这项 3 期研究中，我们将患者随机分配至接受依鲁替尼+来那度胺和地塞米松（依鲁替尼组）或来那度胺和地塞米松单药治疗（对照组）。主要终点是无进展生存期和总缓解率。无进展生存期的主要终点最终结果基于计划的中期分析。
结果：共有 321 例患者被分配至依鲁替尼组，325 例患者被分配至对照组。中位随访 24.5 个月后，依鲁替尼组 1 年无进展生存率为 68%，对照组为 57%；2 年时，两组的无进展生存率分别为 41%和 27%。依鲁替尼组的中位无进展生存期为 19.4 个月，对照组为 14.9 个月（依鲁替尼组疾病进展或死亡的风险比为 0.70；95%置信区间为 0.57 至 0.85；P<0.001）。依鲁替尼组的总缓解率为 79%，对照组为 66%（P<0.001）。两组常见的 3 级或 4 级不良事件为淋巴细胞减少症、中性粒细胞减少症、疲劳和肺炎。依鲁替尼组有 33 例（10%）患者发生输注反应，29 例为 1 级或 2 级。
结论：接受依鲁替尼、来那度胺和地塞米松联合治疗的复发或难治性多发性骨髓瘤患者，疾病进展或死亡的风险相对降低了 30%。（由 Bristol-Myers Squibb 和 AbbVie Biotherapeutics 资助；ELOQUENT-2 ClinicalTrials.gov 编号，NCT01239797。）
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