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抗BCMA CAR T细胞疗法bb2121治疗复发性或难治性多发性骨髓瘤
Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma


Noopur Raje ... 肿瘤 • 2019.05.02
相关阅读
• 用CAR T细胞靶向骨髓瘤 • 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 • 埃罗妥珠单抗治疗多发性骨髓瘤 • CD19 CAR治疗急性淋巴细胞白血病的长期随访研究 • tisagenlecleucel治疗成人复发性或难治性弥漫性大B细胞淋巴瘤

摘要


背景

bb2121是一种靶向B细胞成熟抗原(BCMA)的嵌合抗原受体(CAR)T细胞疗法。临床前研究提示bb2121具有治疗多发性骨髓瘤的潜力。

 

方法

在这项纳入复发性或难治性多发性骨髓瘤患者的1期研究中,在剂量递增阶段,我们以单次输入形式给予患者剂量为50×106、150×106、450×106或800×106的CAR阳性(CAR+)T细胞,在扩展阶段,我们给予患者150×106~450×106 CAR+ T细胞。患者既往接受过至少三线疗法(包括一种蛋白酶体抑制剂和一种免疫调节剂),或者使用两类药物后均表现为难治性疾病。主要终点为安全性。

 

结果

本文报告了最早接受bb2121输入的连续33例患者的结果。数据截止日期是最后一次输入日期后6.2个月。最常见的3级或更高级别事件是血液学毒性作用,包括中性粒细胞减少(85%的患者)、白细胞减少(58%)、贫血(45%)和血小板减少(45%)。共有25例患者(76%)出现了细胞因子释放综合征,其中23例患者(70%)为1或2级,2例患者(6%)的为3级。14例患者(42%)出现了神经毒性作用,其中13例患者(39%)为1或2级。1例患者(3%)出现了可逆的4级神经毒性作用。客观缓解率为85%,包括完全缓解的15例患者(45%)。在完全缓解的15例患者中,6例复发。中位无进展生存期为11.8个月(95%置信区间,6.2~17.8)。出现缓解(部分缓解或更好)且可以对微小残留病变(MRD)进行评价的所有16例患者的状态均为MRD阴性(≤10-4个有核细胞)。CAR T细胞扩增与缓解相关,且CAR T细胞持续至输入后长达1年。

 

结论

我们报告了复发性或难治性多发性骨髓瘤患者接受靶向BCMA的细胞免疫疗法后表现出的初步毒性特征。研究证实了bb2121的抗肿瘤活性(由蓝鸟生物[Bluebird Bio]和赛尔基因[Celgene]资助;CRB-401在ClinicalTrials.gov注册号为NCT02658929)。





作者信息

Noopur Raje, M.D., Jesus Berdeja, M.D., Yi Lin, M.D., Ph.D., David Siegel, M.D., Ph.D., Sundar Jagannath, M.D., Deepu Madduri, M.D., Michaela Liedtke, M.D., Jacalyn Rosenblatt, M.D., Marcela V. Maus, M.D., Ph.D., Ashley Turka, Lyh-Ping Lam, Pharm.D., Richard A. Morgan, Ph.D., Kevin Friedman, Ph.D., Monica Massaro, M.P.H., Julie Wang, Pharm.D., Ph.D., Greg Russotti, Ph.D., Zhihong Yang, Ph.D., Timothy Campbell, M.D., Ph.D., Kristen Hege, M.D., Fabio Petrocca, M.D., M. Travis Quigley, M.S., Nikhil Munshi, M.D., and James N. Kochenderfer, M.D.
From the Massachusetts General Hospital Cancer Center (N.R., M.V.M.), Beth Israel Deaconess Medical Center (J.R.), and Dana–Farber Cancer Institute and Veterans Affairs Boston Healthcare System (N.M.), Boston, and Bluebird Bio, Cambridge (A.T., L.-P.L., R.A.M., K.F., M.M., F.P., M.T.Q.) — all in Massachusetts; Sarah Cannon Research Institute and Tennessee Oncology, Nashville (J.B.); Mayo Clinic, Rochester, MN (Y.L.); Hackensack University Medical Center, Hackensack (D.S.), and Celgene, Summit (J.W., G.R., Z.Y.) — both in New Jersey; Mount Sinai Medical Center, New York (S.J., D.M.); Stanford University Medical Center, Palo Alto (M.L.), and Celgene, San Francisco (T.C., K.H.) — both in California; and the Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (J.N.K.). Address reprint requests to Dr. Kochenderfer at the Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bldg. 10–CRC–Rm. 3-3888, Bethesda, MD 20892, or at kochendj@mail.nih.gov.

 

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