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axicabtagene ciloleucel CAR T细胞疗法治疗难治性大B细胞淋巴瘤
Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma


Sattva S. Neelapu ... 肿瘤 • 2017.12.28
相关阅读
• 悲剧、坚持和机遇——CAR-T疗法的故事 • ASCO 2017报告——血液系统恶性肿瘤

CAR T细胞疗法和恶性淋巴瘤治疗的里程碑

 

侯景周

UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA

 

肿瘤治疗正在进行着革命性的进展。抗原特异性的肿瘤免疫治疗,比如免疫检查点抑制剂和嵌合抗原受体(chimeric antigen receptor,CAR)T细胞疗法,已经为一小部分晚期或复发的肿瘤患者带来长期完全缓解,为治愈肿瘤带来了更多的希望和信心。CAR T CD19对于淋巴细胞白血病的疗效带来了针对不同靶向抗原CAR T的蓬勃发展。据宋永平和刘德龙教授等人的统计分析,截至2017年7月,至少已经有121项来自中国的针对CD19和其他靶点抗原的CAR T临床试验在ClinicalTrials.gov注册1

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摘要


背景

在一项1期临床试验中,一种自体抗CD19嵌合抗原受体(CAR)T细胞疗法axicabtagene ciloleucel(axi-cel)对常规治疗失败后的难治性大B细胞淋巴瘤患者表现出疗效。

 

方法

此项多中心、2期临床试验纳入了111例难治性弥漫性大B细胞淋巴瘤、原发性纵隔B细胞淋巴瘤或转化型滤泡淋巴瘤(transformed follicular lymphoma)患者,他们既往接受过推荐疗法。在接受小剂量环磷酰胺和氟达拉滨进行预处理后,患者接受了每千克体重2×106抗CD19 CAR T细胞的目标剂量。主要终点是客观缓解率(以完全缓解加部分缓解计算)。次要终点包括总生存率、安全性和生物标志物评估。

 

结果

在纳入的111例患者中,110例(99%)患者的axi-cel成功制备,其中101例患者(91%)接受输注。客观缓解率为82%,完全缓解率为54%。中位随访时间15.4个月时,42%的患者持续缓解,40%的患者持续完全缓解。18个月时,总生存率为52%。治疗过程中最常见的3级或更高级别不良事件是中性粒细胞减少(78%)、贫血(43%)和血小板减少(38%)。3级或更高级别的细胞因子释放综合征和神经系统事件发生率分别为13%和28%。3例患者在治疗期间死亡。血液中较高的CAR T细胞水平与肿瘤缓解相关。

 

结论

在这项多中心研究中,难治性大B细胞淋巴瘤患者使用axi-cel进行CAR T细胞治疗,持续缓解率较高,其安全性涉及骨髓抑制、细胞因子释放综合征和神经系统事件(由Kite Pharma及白血病和淋巴瘤学会治疗加速项目[Leukemia and Lymphoma Society Therapy Acceleration Program]资助;ZUMA-1在ClinicalTrials.gov注册号为NCT02348216)。





作者信息

Sattva S. Neelapu, M.D., Frederick L. Locke, M.D., Nancy L. Bartlett, M.D., Lazaros J. Lekakis, M.D., David B. Miklos, M.D., Ph.D., Caron A. Jacobson, M.D., M.M.Sc., Ira Braunschweig, M.D., Olalekan O. Oluwole, M.B., B.S., M.P.H., Tanya Siddiqi, M.D., Yi Lin, M.D., Ph.D., John M. Timmerman, M.D., Patrick J. Stiff, M.D., Jonathan W. Friedberg, M.D., M.M.Sc., Ian W. Flinn, M.D., Ph.D., Andre Goy, M.D., Brian T. Hill, M.D., Ph.D., Mitchell R. Smith, M.D., Ph.D., Abhinav Deol, M.D., Umar Farooq, M.D., Peter McSweeney, M.D., Javier Munoz, M.D., Irit Avivi, M.D., Januario E. Castro, M.D., Jason R. Westin, M.D., Julio C. Chavez, M.D., Armin Ghobadi, M.D., Krishna V. Komanduri, M.D., Ronald Levy, M.D., Eric D. Jacobsen, M.D., Thomas E. Witzig, M.D., Patrick Reagan, M.D., Adrian Bot, M.D., Ph.D., John Rossi, M.S., Lynn Navale, M.S., Yizhou Jiang, Ph.D., Jeff Aycock, B.A., Meg Elias, R.N., B.S.N., David Chang, M.D., Ph.D., Jeff Wiezorek, M.D., and William Y. Go, M.D., Ph.D.
From the University of Texas M.D. Anderson Cancer Center, Houston (S.S.N., J.R.W.); H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (F.L.L., J.C.C.); Washington University and Siteman Cancer Center, St. Louis (N.L.B., A. Ghobadi); University of Miami, Miami (L.J.L., K.V.K.); Stanford University, Stanford (D.B.M., R.L.), City of Hope National Medical Center, Duarte (T.S.), University of California at Los Angeles, Los Angeles (J.M.T.), University of California at San Diego, San Diego (J.E.C.), and Kite Pharma, Santa Monica (A.B., J.R., L.N., Y.J., J.A., M.E., D.C., J.W., W.Y.G.) — all in California; Dana–Farber Cancer Institute, Boston (C.A.J., E.D.J.); Montefiore Medical Center, Bronx (I.B.), and the University of Rochester School of Medicine, Rochester (J.W.F., P.R.) — both in New York; Vanderbilt University Medical Center (O.O.O.) and the Sarah Cannon Research Institute and Tennessee Oncology (I.W.F.), Nashville; Mayo Clinic, Rochester, MN (Y.L., T.E.W.); Loyola University Medical Center, Maywood, IL (P.J.S.); John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ (A. Goy); Cleveland Clinic, Cleveland (B.T.H., M.R.S.); Karmanos Cancer Center, Wayne State University, Detroit (A.D.); University of Iowa Carver College of Medicine, Iowa City (U.F.); Colorado Blood Cancer Institute, Denver (P.M.S.); Banner M.D. Anderson Cancer Center, Gilbert, AZ (J.M.); and Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (I.A.). Address reprint requests to Dr. Neelapu at the University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, or at sneelapu@mdanderson.org.

 

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