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KTE-X19 CAR T细胞疗法治疗复发性或难治性套细胞淋巴瘤
KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma


Michael Wang ... 肿瘤 • 2020.04.02
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摘要


背景

在布鲁顿酪氨酸激酶(BTK)抑制剂治疗期间或之后发生疾病进展的复发性或难治性套细胞淋巴瘤患者的预后不良。KTE-X19是抗CD19嵌合抗原受体(CAR)T细胞疗法,可能对复发性或难治性套细胞淋巴瘤患者有益。

 

方法

在一项多中心、2期试验中,我们在复发性或难治性套细胞淋巴瘤患者中评价了KTE-X19。患者患有既往接受最多5种疗法后复发或难治的疾病;所有患者必须接受过BTK抑制剂治疗。患者接受了白细胞采集术和可选的过渡治疗,之后接受了预处理化疗和KTE-X19单次输入(剂量为2×106 CAR T细胞/kg体重)。主要终点是达到客观缓解(完全或部分缓解)的患者百分比,缓解情况由独立的放射学审核委员会按照Lugano分级进行评估。按照试验方案,我们在60例患者接受治疗和7个月随访之后进行了主要疗效分析。

 

结果

共计74例患者被纳入试验。我们为71例患者制备了KTE-X19,并将其用于了68例患者。主要疗效分析表明,在主要疗效分析的60例患者中,93%(95%置信区间[CI],84~98)达到了客观缓解;67%(95% CI,53~78)达到了完全缓解。在对全部74例患者进行的意向治疗分析中,85%达到了客观缓解;59%达到了完全缓解。在中位12.3个月(范围,7.0~32.3)随访时间,在主要疗效分析的60例患者中,57%处于缓解状态。在12个月时,估计无进展生存率和总生存率分别为61%和83%。常见的3级或更高级别不良事件为血细胞减少(94%的患者)和感染(32%)。3级或更高级别的细胞因子释放综合征和神经系统事件分别发生于15%和31%的患者,这些事件均未导致患者死亡。研究中发生了2起5级感染性不良事件。

 

结论

KTE-X19诱导大多数复发性或难治性套细胞淋巴瘤患者达到了持久缓解。此疗法导致了严重和危及生命的毒性作用,与使用其他CAR T细胞疗法时报告的情况一致(由Kite公司[吉利德集团的一家公司]资助;ZUMA-2在ClinicalTrials.gov注册号为NCT02601313)。





作者信息

Michael Wang, M.D., Javier Munoz, M.D., Andre Goy, M.D., Frederick L. Locke, M.D., Caron A. Jacobson, M.D., Brian T. Hill, M.D., Ph.D., John M. Timmerman, M.D., Houston Holmes, M.D., Samantha Jaglowski, M.D., Ian W. Flinn, M.D., Ph.D., Peter A. McSweeney, M.D., David B. Miklos, M.D., John M. Pagel, M.D., Ph.D., Marie-Jose Kersten, M.D., Noel Milpied, M.D., Henry Fung, M.D., Max S. Topp, M.D., Roch Houot, M.D., Amer Beitinjaneh, M.D., Weimin Peng, Ph.D., Lianqing Zheng, Ph.D., John M. Rossi, M.S., Rajul K. Jain, M.D., Arati V. Rao, M.D., and Patrick M. Reagan, M.D.
From the University of Texas M.D. Anderson Cancer Center, Houston (M.W.), and Texas Oncology, Dallas (H.H.); Banner M.D. Anderson Cancer Center, Gilbert, AZ (J.M.); John Theurer Cancer Center, Hackensack, NJ (A.G.); Moffitt Cancer Center, Tampa (F.L.L.), and the University of Miami, Miami (A.B.) — both in Florida; Dana–Farber Cancer Institute, Boston (C.A.J.); Cleveland Clinic Foundation, Cleveland (B.T.H.), and the Ohio State University Comprehensive Cancer Center, Columbus (S.J.); David Geffen School of Medicine at UCLA, Los Angeles (J.M.T.), Stanford University School of Medicine, Stanford (D.B.M.), and Kite, a Gilead company, Santa Monica (W.P., L.Z., J.M.R., R.K.J., A.V.R.) — all in California; Sarah Cannon Research Institute–Tennessee Oncology, Nashville (I.W.F.); Colorado Blood Cancer Institute, Denver (P.A.M.); Swedish Cancer Institute, Seattle (J.M.P.); the Academic Medical Center, University of Amsterdam, Amsterdam, for the Lunenburg Lymphoma Phase I/II Consortium (M.-J.K.); Centre Hospitalier Universitaire (CHU) Bordeaux, Service d’Hematologie et Therapie Cellulaire, Bordeaux (N.M.), and CHU Rennes, INSERM French Blood Establishment, Rennes (R.H.) — both in France; Fox Chase Cancer Center, Philadelphia (H.F.); Universitätsklinikum Würzburg, Würzburg, Germany (M.S.T.); and the University of Rochester Medical Center, Rochester, NY (P.M.R.). Address reprint requests to Dr. Wang at the Department of Lymphoma–Myeloma, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, or at miwang@mdanderson.org.

 

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