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CD19 CAR治疗急性淋巴细胞白血病的长期随访研究
Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia


Jae H. Park ... 肿瘤 • 2018.02.01
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CAR T治疗复发/难治性急性淋巴细胞白血病具有长效

 

刘德龙

New York Medical College and Westchester Medical Center

 

即使在今天,复发/难治性(R/R)急性淋巴细胞白血病(ALL)成人患者的预后仍然令人沮丧。使用挽救性化疗,R/R ALL患者中只有29%(范围,18%~44%)可被诱导为完全缓解(CR),中位总生存期(OS)为4个月(范围,2~6个月)。

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摘要


背景

在复发性B细胞急性淋巴细胞白血病(ALL)患者中,CD19特异性嵌合抗原受体(CAR)T细胞疗法的初次诱导缓解率高,部分患者可实现长期缓解。

 

方法

我们在纪念斯隆·凯特林癌症中心(Memorial Sloan Kettering Cancer Center,MSKCC)接受表达19-28z CAR的自体T细胞输入的复发性B细胞ALL成人患者中,开展了一项1期临床试验,评估了安全性和远期结局及其与人口统计学、临床和疾病特征的相关性。

 

结果

共53例成人患者接受了在MSKCC制备的19-28z CAR T细胞治疗。输入后,53例患者中有14例出现了重度细胞因子释放综合征(26%;95%置信区间[CI],15~40);1例患者死亡。83%的患者完全缓解。中位随访时间29个月(范围,1~65个月)时,中位无事件生存期为6.1个月(95% CI,5.0~11.5),中位总生存期为12.9个月(95% CI,8.7~23.4)。治疗前疾病负荷低(<5%骨髓原始细胞)的患者缓解持续时间和生存期显著较好,中位无事件生存期为10.6个月(95% CI,5.9至未达到),中位总生存期为20.1个月(95% CI,8.7至未达到)。与疾病负荷低的患者相比,疾病负荷较高(≥5%骨髓原始细胞或髓外疾病)患者的细胞因子释放综合征和神经毒性事件的发生率较高,远期生存期较短。

 

结论

整个队列的中位总生存期为12.9个月。疾病负荷低的患者中位总生存期为20.1个月,并且与疾病负荷较高的患者相比,在接受19-28z CAR T细胞输注后,前者的细胞因子释放综合征和神经毒性事件的发生率显著较低(由英联邦癌症研究基金会[Commonwealth Foundation for Cancer Research]等资助;在ClinicalTrials.gov注册号为NCT01044069)。





作者信息

Jae H. Park, M.D., Isabelle Rivière, Ph.D., Mithat Gonen, Ph.D., Xiuyan Wang, Ph.D., Brigitte Sénéchal, Ph.D., Kevin J. Curran, M.D., Craig Sauter, M.D., Yongzeng Wang, Ph.D., Bianca Santomasso, M.D., Ph.D., Elena Mead, M.D., Mikhail Roshal, M.D., Peter Maslak, M.D., Marco Davila, M.D., Ph.D., Renier J. Brentjens, M.D., Ph.D., and Michel Sadelain, M.D., Ph.D.
From the Leukemia Service, Department of Medicine (J.H.P., C.S., P.M., R.J.B.), the Michael G. Harris Cell Therapy and Cell Engineering Facility (I.R., X.W., B. Sénéchal, Y.W.), the Center for Cell Engineering (J.H.P., I.R., X.W., R.J.B., M.S.), and the Departments of Epidemiology and Biostatistics (M.G.), Pediatrics (K.J.C.), Neurology (B. Santomasso), Anesthesiology and Critical Care Medicine (E.M.), and Pathology (M.R.), Memorial Sloan Kettering Cancer Center, and the Department of Medicine, Joan and Sanford Weill Medical College of Cornell University (J.H.P., C.S., R.J.B.) — all in New York; and the Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center, Tampa, FL (M.D.). Address reprint requests to Dr. Sadelain at the Memorial Sloan Kettering Cancer Center, 1275 York Ave., Box 184, New York, NY 10065, or at m-sadelain@ski.mskcc.org.

 

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