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达雷木单抗联合硼替佐米、美法仑和泼尼松用于未经治疗的骨髓瘤
Daratumumab plus Bortezomib, Melphalan, and Prednisone for Untreated Myeloma


María-Victoria Mateos ... 肿瘤 • 2018.02.08
相关阅读
• 骨髓瘤的一线免疫疗法 • 达雷木单抗、来那度胺和地塞米松治疗多发性骨髓瘤的研究 • 达雷木单抗联合治疗对复发性骨髓瘤有效

摘要


背景

硼替佐米、美法仑、泼尼松联合用药是针对不适宜自体干细胞移植的、新诊断的多发性骨髓瘤患者的标准治疗方案。研究表明在复发性或难治性多发性骨髓瘤患者中,达雷木单抗(daratumumab)和标准治疗方案联用有效。

 

方法

在3期临床试验中,我们随机分配706例不适宜干细胞移植的新诊断多发性骨髓瘤患者接受9个周期的硼替佐米、美法仑、泼尼松单独合用治疗(对照组)或与达雷木单抗联用治疗(达雷木单抗组),直至出现疾病进展。研究主要终点是无进展生存期。

 

结果

预设中期分析的中位随访时间16.5个月内,达雷木单抗组的18个月无进展生存率为71.6% (95%置信区间[CI],65.5~76.8),对照组为50.2%(95% CI,43.2~56.7)(疾病进展或死亡风险比,0.50;95% CI,0.38~0.65;P<0.001)。达雷木单抗组的总缓解率为90.9%,而对照组为73.9%(P<0.001),完全缓解或状况更好的比例(包括严格完全缓解)分别为42.6%和24.4%(P<0.001)。在达雷木单抗组中,22.3%的患者为微小残留病变阴性(阈值为每105个白细胞中有1个肿瘤细胞),而对照组为6.2%(P<0.001)。最常见的3级或4级不良事件为血液学事件,其中包括中性粒细胞减少症(达雷木单抗组39.9%的患者发生,而对照组38.7%的患者发生)、血小板减少症(分别为34.4%和37.6%)、贫血(分别为15.9%和19.8%)。达雷木单抗组的3级或4级感染率为23.1%,而对照组为14.7%;因感染终止治疗率分别为0.9%和1.4%。27.7%的患者发生达雷木单抗相关输液反应。

 

结论

在不适宜干细胞移植的新诊断多发性骨髓瘤患者中,达雷木单抗联合硼替佐米、美法仑、泼尼松治疗与无达雷木单抗的相同治疗方案相比,降低了疾病进展或死亡风险。含达雷木单抗的治疗方案增加了3级或4级感染(由杨森研发[Janssen Research and Development]资助;ALCYONE在ClinicalTrials.gov注册号为NCT02195479)。





作者信息

María-Victoria Mateos, M.D., Meletios A. Dimopoulos, M.D., Michele Cavo, M.D., Kenshi Suzuki, M.D., Andrzej Jakubowiak, M.D., Stefan Knop, M.D., Chantal Doyen, M.D., Paulo Lucio, M.D., Zsolt Nagy, M.D., Polina Kaplan, M.D., Ludek Pour, M.D., Mark Cook, M.D., Sebastian Grosicki, M.D., Andre Crepaldi, M.D., Anna M. Liberati, M.D., Philip Campbell, M.D., Tatiana Shelekhova, M.D., Sung-Soo Yoon, M.D., Genadi Iosava, Ph.D., Tomoaki Fujisaki, M.D., et al., for the ALCYONE Trial Investigators*
From University Hospital of Salamanca–Instituto de Investigación Biomédica de Salamanca, Salamanca (M.-V.M.), and Clínica Universidad de Navarra–Centro de Investigación Médica Aplicada, Instituto de Investigación Sanitaria de Navarra, Centro de Investigación Biomédica en Red de Cáncer, Pamplona (J.S.-M.) — both in Spain; National and Kapodistrian University of Athens, Athens (M.A.D.); the Institute of Hematology, Department of Experimental, Diagnostic, and Specialty Medicine, University of Bologna, Bologna (M. Cavo), and Azienda Ospedaliera “Santa Maria,” Terni (A.M.L.) — both in Italy; Japanese Red Cross Medical Center, Department of Hematology, Tokyo (K.S.); University of Chicago Medical Center, Chicago (A.J.); Würzburg University Medical Center, Würzburg, Germany (S.K.); Université Catholique de Louvain (UCL), Centre Hospitalier Universitaire UCL Namur, Yvoir (C.D.), and Janssen Research and Development, Beerse (W.D.) — both in Belgium; Champalimaud Center for the Unknown, Lisbon, Portugal (P.L.); Semmelweis Egyetem, Budapest, Hungary (Z.N.); Dnepropetrovsk City Clinical Hospital #4, Dnepropetrovsk, Ukraine (P.K.); University Hospital Brno, Brno, Czech Republic (L.P.); University Hospitals Birmingham NHS Foundation Trust, Birmingham (M. Cook), and Leicester Royal Infirmary–Haematology, Leicester (M.G.) — both in the United Kingdom; the Department of Cancer Prevention, School of Public Health, Silesian Medical University, Katowice, Poland (S.G.); Clínica de Tratamento E, Cuiaba, Brazil (A.C.); Andrew Love Cancer Centre, Geelong, VIC, Australia (P.C.); Clinic of Professional Pathology, Saratov, Russia (T.S.); the Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea (S.-S.Y.); LTD “Medinvent” Institute of Health, Tbilisi, Georgia (G.I.); Matsuyama Red Cross Hospital, Matsuyama, Japan (T.F.); Janssen Research and Development, Spring House, PA (C.C., R.C., W.C., M.Q.); and Janssen Research and Development, Raritan, NJ (J.W., H.N.). Address reprint requests to Dr. Mateos at Paseo de San Vicente 58, 37007 Salamanca, Spain, or at mvmateos@usal.es. *A complete list of investigators in the ALCYONE trial is provided in the Supplementary Appendix, available at NEJM.org.

 

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