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idecabtagene vicleucel治疗复发性和难治性多发性骨髓瘤
Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma


Nikhil C. Munshi ... 肿瘤 • 2021.02.25
相关阅读
• 多发性骨髓瘤的CAR T细胞疗法 • 抗BCMA CAR T细胞疗法bb2121治疗复发性或难治性多发性骨髓瘤 • 达雷妥尤单抗联合硼替佐米、美法仑和泼尼松用于未经治疗的骨髓瘤 • 来那度胺、硼替佐米和地塞米松联合移植治疗骨髓瘤的研究

摘要


背景

idecabtagene vicleucel(ide-cel,也称为bb2121)是B细胞成熟抗原导向的嵌合抗原受体(CAR)T细胞疗法,该疗法在复发性和难治性多发性骨髓瘤患者中显示出临床活性,同时有符合预期的CAR T细胞毒性。

 

方法

在此项2期研究中,我们试图证实ide-cel对复发性和难治性骨髓瘤患者的疗效和安全性。本试验纳入接受过至少三种治疗方案(包括一种蛋白酶体抑制剂、一种免疫调节剂和一种抗CD38抗体)的患者。患者接受ide-cel的目标剂量为150×106~450×106 个CAR阳性(CAR+)T细胞。主要终点是总体缓解(部分缓解或更好疗效);关键次要终点是完全缓解或更好疗效(包括完全和严格完全缓解)。

 

结果

在本试验纳入的140例患者中,128例接受了ide-cel治疗。在中位13.3个月随访期间,128例患者中的94例(73%)达到缓解,128例患者中的42例(33%)达到完全缓解或更好疗效。33例患者被证实为微小残留病变(MRD)阴性(<10-5个有核细胞),在接受治疗的所有128例患者中占26%,在达到完全缓解或更好疗效的42例患者中占79%。中位无进展生存期为8.8个月(95% CI,5.6~11.6)。在128例接受治疗的患者中,常见毒性作用包括发生于117例患者的中性粒细胞减少症(91%)、发生于89例患者的贫血(70%)和发生于81例患者的血小板减少症(63%)。据报告,107例患者(84%)发生了细胞因子释放综合征,其中7例(5%)发生3级或3级以上事件。23例患者(18%)发生了神经毒性作用,其中4例患者(3%)为3级;未发生3级以上的神经毒性作用。在输注后6个月和12个月时,细胞动力学分析分别证实了49例患者中29例(59%)和11例患者中4例(36%)的CAR+ T细胞。

 

结论

ide-cel使大多数之前接受过大量治疗的难治性和复发性骨髓瘤患者达到缓解;接受治疗的患者中有26%达到MRD阴性。几乎所有患者都发生了3级或4级毒性作用,最常见的是血液学毒性作用和细胞因子释放综合征(由蓝鸟生物[bluebird bio]和百时美施贵宝公司的Celgene出资;KarMMa在ClinicalTrials.gov注册号为NCT03361748)。





作者信息

Nikhil C. Munshi, M.D., Larry D. Anderson, Jr., M.D., Ph.D., Nina Shah, M.D., Deepu Madduri, M.D., Jesús Berdeja, M.D., Sagar Lonial, M.D., Noopur Raje, M.D., Yi Lin, M.D., Ph.D., David Siegel, M.D., Ph.D., Albert Oriol, M.D., Philippe Moreau, M.D., Ibrahim Yakoub-Agha, M.D., Ph.D., Michel Delforge, M.D., Michele Cavo, M.D., Hermann Einsele, M.D., Hartmut Goldschmidt, M.D., Katja Weisel, M.D., Alessandro Rambaldi, M.D., Donna Reece, M.D., Fabio Petrocca, M.D., Monica Massaro, M.P.H., Jamie N. Connarn, Ph.D., Shari Kaiser, Ph.D., Payal Patel, Ph.D., Liping Huang, Ph.D., Timothy B. Campbell, M.D., Ph.D., Kristen Hege, M.D., and Jesús San-Miguel, M.D., Ph.D.
From the Jerome Lipper Multiple Myeloma Center, Dana–Farber Cancer Institute (N.C.M.), the Veterans Affairs Boston Healthcare System, Harvard Medical School (N.C.M.), and Massachusetts General Hospital (N.R.), Boston, and bluebird bio, Cambridge (F.P., M.M.) — all in Massachusetts; Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas (L.D.A.); the University of California, San Francisco, San Francisco (N.S.); Icahn School of Medicine at Mount Sinai, New York (D.M.); Sarah Cannon Research Institute and Tennessee Oncology, Nashville (J.B.); Emory School of Medicine, Atlanta (S.L.); Mayo Clinic, Rochester, MN (Y.L.); Hackensack University Medical Center, Hackensack (D.S.), and Bristol-Myers Squibb, Princeton (J.N.C., S.K., P.P., L.H., T.B.C., K.H.) — both in New Jersey; Institut Josep Carreras and Institut Catala d’Oncologia, Hospital Germans Trias i Pujol, Badalona (A.O.), and Clinica 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; Centre Hospitalier Universitaire (CHU) de Nantes, Nantes (P.M.), and CHU de Lille, University of Lille, INSERM Unité 1286, Institute for Translational Research in Inflammation, Lille (I.Y.-A.) — both in France; University Hospital Leuven, Leuven, Belgium (M.D.); “Seràgnoli” Institute of Hematology, Bologna University School of Medicine, Bologna (M.C.), the Department of Oncology and Hematology, University of Milan, Milan (A.R.), and Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo (A.R.) — all in Italy; University Hospital of Würzburg, Würzburg (H.E.), University Hospital Heidelberg (H.G.) and the National Center for Tumor Diseases (H.G.), Heidelberg, the University Medical Center Hamburg-Eppendorf, Hamburg (K.W.), and Universitätsklinikum Tübingen, Tübingen (K.W.) — all in Germany; and Princess Margaret Cancer Centre, Toronto (D.R.). Address reprint requests to Dr. Munshi at the Jerome Lipper Multiple Myeloma Center, Dana–Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave., Boston, MA 02215, or at nikhil_munshi@dfci.harvard.edu

 

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