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tisagenlecleucel治疗成人复发性或难治性弥漫性大B细胞淋巴瘤
Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma


Stephen J. Schuster ... 肿瘤 • 2019.01.03
相关阅读
• ASCO 2019报告——恶性血液病 • 抗BCMA CAR T细胞疗法bb2121治疗复发性或难治性多发性骨髓瘤 • tisagenlecleucel治疗儿童和年轻成人B细胞淋巴细胞白血病

CAR T治疗淋巴瘤:单点制备,全球运送,疗效有保障

 

杨建民

海军军医大学附属长海医院血液内科

 

近年来,随着靶向CD19的CAR T细胞在难治/复发B细胞淋巴瘤的挽救性治疗中取得神奇疗效,并在全球多个研究中心的临床试验中得以证实,一个急需回答的问题就是:是否可以像其他生物药物一样,建立单一的CAR T细胞制备中心,利用冷链向全球递送细胞?运输过程又会对CAR T细胞的临床疗效与毒副作用产生何种影响?

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摘要


背景

经一线和二线治疗表现为难治性或干细胞移植后复发的弥漫性大B细胞淋巴瘤患者提示预后不良。嵌合抗原受体(CAR)T细胞疗法tisagenlecleucel靶向并清除表达CD19的B细胞,tisagenlecleucel在一项单中心、2a期研究中显示出对B细胞淋巴瘤的疗效。

 

方法

我们在不适合接受自体造血干细胞移植或移植后疾病进展的复发性或难治性弥漫性大B细胞淋巴瘤成人患者中,应用统一制备的tisagenlecleucel,开展了一项国际性、2期关键研究。主要终点为由一个独立审核委员会判定的最佳总缓解率(即完全或部分缓解的患者百分比)。

 

结果

总共93例患者接受了tisagenlecleucel输注,并被纳入疗效评价。从输注至数据截止的中位时间为14个月(范围,0.1~26个月)。最佳总缓解率为52%(95% 置信区间[CI],41%~62%);40%的患者完全缓解,12%部分缓解。各预后亚组的缓解率一致。在初次缓解后12个月时,无复发生存率估计为65%(在完全缓解的患者中为79%)。最常见的特别关注的3级或4级不良事件包括细胞因子释放综合征(22%)、神经系统事件(12%)、持续超过28天的血细胞减少(32%)、感染(20%)和中性粒细胞减少性发热(14%)。输注后30日内,3例患者死于疾病进展。无任何归因于由tisagenlecleucel、细胞因子释放综合征或脑水肿引起的死亡事件。在CD19或免疫检查点相关蛋白表达方面,在各缓解组之间未见差异。

 

结论

在CAR T细胞疗法治疗复发性或难治性弥漫性大B细胞淋巴瘤成人患者的这项国际性研究中,使用tisagenlecleucel达到了较高的持久缓解率(由诺华资助;JULIET在ClinicalTrials.gov注册号为NCT02445248)。





作者信息

Stephen J. Schuster, M.D., Michael R. Bishop, M.D., Constantine S. Tam, M.D., Edmund K. Waller, M.D., Ph.D., Peter Borchmann, M.D., Joseph P. McGuirk, D.O., Ulrich Jäger, M.D., Samantha Jaglowski, M.D., Charalambos Andreadis, M.D., Jason R. Westin, M.D., Isabelle Fleury, M.D., Veronika Bachanova, M.D., Ph.D., S. Ronan Foley, M.D., P. Joy Ho, M.B., B.S., D.Phil., Stephan Mielke, M.D., John M. Magenau, M.D., Harald Holte, M.D., Ph.D., Serafino Pantano, Ph.D., Lida B. Pacaud, M.D., Rakesh Awasthi, Ph.D., Jufen Chu, Ph.D., Özlem Anak, M.D., Gilles Salles, M.D., Ph.D., and Richard T. Maziarz, M.D. for the JULIET Investigators*
From the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (S.J.S.); the Hematopoietic Cellular Therapy Program, University of Chicago Medicine, Chicago (M.R.B.); Peter MacCallum Cancer Centre, St. Vincent’s Hospital and University of Melbourne, Melbourne, VIC (C.S.T.), and the Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Sydney (P.J.H.) — both in Australia; Winship Cancer Institute of Emory University, Bone Marrow and Stem Cell Transplant Center, Atlanta (E.K.W.); the Department of Hematology and Oncology, University Hospital of Cologne, Cologne (P.B.), and the Würzburg University Medical Center, Center for Allogeneic Stem Cell Transplantation, Würzburg (S.M.) — both in Germany; the Division of Hematologic Malignancies and Cellular Therapeutics, University of Kansas Cancer Center, Kansas City (J.P.M.); the Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna (U.J.); James Cancer Hospital and Solove Research Institute, Ohio State University Comprehensive Cancer Center, Columbus (S.J.); the Department of Hematology and Blood and Marrow Transplant, University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (C.A.); the Department of Lymphoma and Myeloma, Division of Cancer Medicine, University of Texas M.D. Anderson Cancer Center, Houston (J.R.W.); Maisonneuve-Rosemont Hospital, University of Montreal, Montreal (I.F.), and the Juravinski Hospital and Cancer Centre, McMaster University, Hamilton, ON (S.R.F.) — both in Canada; the Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis (V.B.); Karolinska Institutet and University Hospital, Department of Laboratory Medicine/Department of Cell Therapy and Allogeneic Stem Cell Transplantation, Stockholm (S.M.); University of Michigan Comprehensive Cancer Center, Ann Arbor (J.M.M.); the Department of Oncology, Oslo University Hospital, Oslo (H.H.); Novartis Pharma, Basel, Switzerland (S.P., O.A.); Novartis Pharmaceuticals (L.B.P., J.C.) and Novartis Institutes for BioMedical Research (R.A.), East Hanover, NJ; the Department of Hematology, Hospices Civils de Lyon, Université de Lyon, Lyon, France (G.S.); and the Center for Hematologic Malignancies, Oregon Health and Science University Knight Cancer Institute, Portland (R.T.M.). Address reprint requests to Dr. Schuster at the Perelman Center for Advanced Medicine, University of Pennsylvania, 3400 Civic Center Blvd., Philadelphia, PA 19104, or at stephen.schuster@uphs.upenn.edu. *A complete list of the JULIET investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

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