梅西格多米德加上德克萨米他治疗复发性和耐火性多发性髓瘤
Paul G Richardson1, Suzanne Trudel1, Rakesh Popat1
1From Dana-Farber Cancer Institute, Boston (P.G.R.); the Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto (S.T.), and Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB (N.J.B.) - both in Canada; NIHR UCLH Clinical Research Facility, University College London Hospitals NHS Foundation Trust (R.P.), the Institute of Cancer Research (C.P.), and the Royal Marsden NHS Foundation Trust (C.P.), London, and the Department of Clinical Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford (K.R.) - all in the United Kingdom; University Hospital of Salamanca/IBSAL, Salamanca (M.-V.M.), the Department of Hematology, Hospital 12 de Octubre, Department of Medicine, School of Medicine, Complutense University, H12O-CNIO Clinical Research Unit, CIBERONC, Madrid (J.M.-L.), Hospital Universitari La Fe, Valencia (M.A.), Institut Català d'Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Badalona (A.O.), Clínica Universidad de Navarra, CIMA, IDISNA, CIBERONC, Pamplona (P.R.O.), and Hospital San Pedro de Alcántara, Cáceres (I.C.-A.) - all in Spain; the Department of Hematology, Rigshospitalet, Copenhagen (A.J.V.); St. Vincent's Hospital Melbourne, University of Melbourne, Melbourne, VIC, Australia (H.Q.); the Department of Lymphoma and Myeloma, University of Texas M.D. Anderson Cancer Center, Houston (R.Z.O.); Winship Cancer Institute, Emory University, Atlanta (S. Lonial); Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope, Duarte, CA (C.K.); Sungkyunkwan University, Samsung Medical Center, Seoul, South Korea (K.K.); Sarah Cannon Research Institute, Nashville (J.G.B.); Celgene International, a Bristol-Myers Squibb Company, Boudry, Switzerland (A.S., T.P.); and Bristol Myers Squibb, Princeton, NJ (J.P., S. Li, J.G., L.W., M.L., D.W.P., M.A., P.M., J.K., M.P.).
梅西格多米德与德克萨米他联合治疗复发性和耐火性多发性骨髓瘤有望出现. 这种新型的口服疗法在重度预治疗的患者中显示出显著的整体反应率.
科学领域:
- 血液学 血液学 血液学
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 多发性骨髓瘤仍然是一个无法治愈的血液恶性瘤,尽管有进展.
- 梅西格多米德是一种新型的cereblon E3泛素酶调节剂,在临床前研究中表现出强大的抗髓瘤活性.
- 它在对莱纳利多米德和波马利多米德等现有疗法耐药的模型中显示出有效性.
研究的目的:
- 评估口服梅西格多米德与德克萨米他联合使用的安全性,药理动力学和疗效.
- 为了确定梅西格多米德和德克萨米他的推第二阶段剂量和时间表.
- 评估复发性和耐火性多发性髓瘤患者的整体应答率和生存结果.
主要方法:
- 一个涉及剂量升级 (第一阶段) 和剂量扩展 (第二阶段) 队列的1-2期研究.
- 患者在28天的循环中接受了口服梅西格多米德和甲.
- 评估了安全性,耐受性,药理动力学和疗效 (总体反应,反应持续时间,无进展生存期).
主要成果:
- 推的2期剂量是1.0毫克的梅西格多米德每日一次,每周期21天.
- 在第二阶段,101名重度预治疗的患有三重类耐火性多发性骨髓瘤的患者被纳入.
- 在41%的患者中观察到整体反应,反应的中位持续时间为7.6个月,中位无进展生存时间为4.4个月.
结论:
- 梅西格多米德和德克萨米他的全口服组合在严重预治疗多发性骨髓瘤的患者中显示出有前途的疗效.
- 与治疗相关的不良事件主要是髓毒性影响,大多是可逆的.
- 这种组合代表了复发性和耐火性多发性髓瘤患者的潜在新疗法选择.
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