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tisagenlecleucel治疗儿童和年轻成人B细胞淋巴细胞白血病
Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia


Shannon L. Maude ... 肿瘤 妇产科和儿科 • 2018.02.01
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• CD19 CAR治疗急性淋巴细胞白血病的长期随访研究 • 利妥昔单抗改善成人急性淋巴细胞白血病的结局 • 利妥昔单抗治疗成人B系急性淋巴细胞白血病 • 博纳吐单抗和化疗在进展期急性淋巴细胞白血病治疗中的比较研究 • 悲剧、坚持和机遇——CAR-T疗法的故事 • 慢性淋巴细胞白血病的CAR-T细胞疗法

摘要


背景

在一项单中心1~2a期研究中,对于患复发性或难治性B细胞急性淋巴细胞白血病(ALL)的儿童和年轻成人,使用tisagenlecleucel这种抗CD19嵌合抗原受体(CAR)T细胞疗法,获得了高完全缓解率。与治疗有关的毒性作用虽然严重,但大部分是可逆的。

 

方法

我们在患CD19+复发性或难治性B细胞ALL的儿童和年轻成人中开展了一项tisagenlecleucel的单队列、25个中心的全球性2期研究。主要终点是3个月内的总缓解率(完全缓解率或伴血细胞不完全恢复的完全缓解率)。

 

结果

为进行这项计划中的分析,75例患者接受了tisagenlecleucel输入并可进行疗效评估。3个月内的总缓解率是81%;根据流式细胞术的测定结果,所有对治疗产生应答的患者微小残留病变均为阴性。6个月时的无事件生存率和总生存率分别为73%(95%置信区间 [CI],60~82)和90%(95% CI,81~95),12个月时的无事件生存率和总生存率分别为50%(95% CI,35~64)和 76%(95% CI,63~86)。未达到中位缓解持续时间。观察到tisagenlecleucel在血液内的持续期长达20个月之久。73%的患者出现了疑似与tisagenlecleucel相关的3级或4级不良事件。77%的患者出现了细胞因子释放综合征,其中48%接受了托珠单抗治疗。40%的患者出现了神经系统事件,采用支持性疗法对这些事件进行了管理,没有脑水肿的报告。

 

结论

在这项CAR T细胞疗法全球性研究中,复发性或难治性B细胞ALL儿童和年轻成人患者单次输注tisagenlecleucel后,获得了长期持续缓解并伴有一过性高级别毒性效应(由诺华制药提供资助;ClinicalTrials.gov注册号为NCT02435849)。





作者信息

Shannon L. Maude, M.D., Ph.D., Theodore W. Laetsch, M.D., Jochen Buechner, M.D., Ph.D., Susana Rives, M.D., Ph.D., Michael Boyer, M.D., Henrique Bittencourt, M.D., Ph.D., Peter Bader, M.D., Michael R. Verneris, M.D., Heather E. Stefanski, M.D., Ph.D., Gary D. Myers, M.D., Muna Qayed, M.D., Barbara De Moerloose, M.D., Ph.D., Hidefumi Hiramatsu, M.D., Ph.D., Krysta Schlis, M.D., Kara L. Davis, D.O., Paul L. Martin, M.D., Ph.D., Eneida R. Nemecek, M.D., Gregory A. Yanik, M.D., Christina Peters, M.D., Andre Baruchel, M.D., et al.
From the Departments of Pediatrics (S.L.M., S.A.G.) and Pathology and Laboratory Medicine (C.H.J., B.L.L.), Perelman School of Medicine, and Abramson Cancer Center (C.H.J., B.L.L.), University of Pennsylvania, and the Division of Oncology, Center for Childhood Cancer Research and Cancer Immunotherapy Program, Children’s Hospital of Philadelphia (S.L.M., S.A.G.) — all in Philadelphia; the Department of Pediatrics and Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, and the Pauline Allen Gill Center for Cancer and Blood Disorders, Children’s Health, Dallas (T.W.L.); the Department of Pediatric Hematology and Oncology, Oslo University Hospital, Oslo (J.B.); the Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu Barcelona, Barcelona (S.R.); the Department of Pediatrics and Internal Medicine, University of Utah, Salt Lake City (M.B.); the Department of Pediatrics, Faculty of Medicine, University of Montreal, and the Hematology Oncology Division and Charles-Bruneau Cancer Center, Centre Hospitalier Universitaire Sainte-Justine Research Center, Montreal (H.B.), and the Division of Haematology/Oncology/Bone Marrow Transplantation, Hospital for Sick Children, Toronto (J.K.) — all in Canada; the Division of Stem Cell Transplantation and Immunology, Hospital for Children and Adolescents, University Hospital Frankfurt, Frankfurt, Germany (P.B.); the Division of Pediatric Blood and Marrow Transplant, University of Minnesota, Minneapolis (M.R.V., H.E.S.); Children’s Mercy Hospital and Clinics, Kansas City, MO (G.D.M.); Aflac Cancer and Blood Disorders Center, Emory University, Atlanta (M.Q.); the Department of Pediatric Hematology–Oncology and Stem Cell Transplantation, Ghent University Hospital, and the Cancer Research Institute Ghent (CRIG), Ghent, Belgium (B.D.M.); the Department of Pediatrics, Graduate School of Medicine Kyoto University, Kyoto, Japan (H.H.); the Department of Pediatrics, Stanford University School of Medicine, Stanford (K. Schlis, K.L.D.), and the Division of Hematology, Oncology, Blood and Marrow Transplant, Children’s Hospital Los Angeles, USC Keck School of Medicine, Los Angeles (M.A.P.) — all in California; the Division of Pediatric Blood and Marrow Transplant, Duke University Medical Center, Durham, NC (P.L.M.); Oregon Health and Science University, Portland (E.R.N.); C.S. Mott Children’s Hospital, Ann Arbor, MI (G.A.Y.); the Stem Cell Transplantation Unit, St. Anna Children’s Hospital, Vienna (C.P.); University Hospital Robert Debré and University Paris Diderot (A. Baruchel), and Saint-Louis Hospital and University Paris Diderot (N.B.), Paris; the Royal Children’s Hospital, Melbourne, VIC, Australia (F.M.); Clinica Pediatrica Universita degli Studi di Milano Bicocca, Monza, Italy (A. Balduzzi); and Novartis Pharmaceuticals (P.W., T.T., M.L., Y.Z., K. Sen, D.L.) and Novartis Institutes for Biomedical Research (K.T.M.) — both in East Hanover, NJ. Address reprint requests to Dr. Maude at 3012 Colket Translational Research Bldg., 3501 Civic Center Blvd., Philadelphia, PA 19104, or at maude@email.chop.edu.

 

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