CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
侵袭性 B 细胞淋巴瘤的二线 Tisagenlecleucel 治疗与标准治疗比较
英文原题：Second-Line Tisagenlecleucel or Standard Care in Aggressive B-Cell Lymphoma.
查看英文原题
Second-Line Tisagenlecleucel or Standard Care in Aggressive B-Cell Lymphoma.
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研究概要
在该试验中，tisagenlecleucel 并不优于标准挽救治疗。需要进一步研究以评估哪些患者可能从每种方法中获得最大获益。（由诺华资助；BELINDA ClinicalTrials.gov 注册号，NCT03570892。）
研究思路结论见上方概要
背景
侵袭性B细胞非霍奇金淋巴瘤患者若对一线治疗无应答或在12个月内进展，其结局较差。Tisagenlecleucel是一种抗CD19CAR-T 细胞疗法，获批用于至少接受过两线治疗的弥漫性大B细胞淋巴瘤。
方法
我们开展了一项国际性3期试验，纳入对一线治疗难治或在12个月内进展的侵袭性淋巴瘤患者。患者被随机分配接受tisagenlecleucel联合可选桥接治疗（tisagenlecleucel组）或挽救性化疗联合自体造血干细胞移植（HSCT）（标准治疗组）。主要终点为无事件生存期，定义为从随机化至第12周评估时或之后出现稳定或进展性疾病或死亡的时间。若在第12周评估时或之后发生定义的事件，则允许交叉接受tisagenlecleucel。其他终点包括缓解和安全。
结果
共有322例患者接受了随机分组。基线时，tisagenlecleucel组中高级别淋巴瘤患者的比例高于标准治疗组（24.1% vs. 16.9%），国际预后指数评分（范围0至5分，评分越高提示预后越差）为2分或以上的患者比例同样更高（65.4% vs. 57.5%）。tisagenlecleucel组中95.7%的患者接受了tisagenlecleucel治疗；标准治疗组中32.5%的患者接受了自体HSCT。从白细胞分离术到tisagenlecleucel输注的中位时间为52天。tisagenlecleucel组中25.9%的患者在第6周出现淋巴瘤进展，而标准治疗组为13.8%。两组的中位无事件生存期均为3.0个月（tisagenlecleucel组发生事件或死亡的风险比为1.07；95%置信区间为0.82至1.40；P = 0.61）。tisagenlecleucel组46.3%的患者出现缓解，标准治疗组为42.5%。tisagenlecleucel组有10例患者、标准治疗组有13例患者因不良事件死亡。
展开英文摘要原文
BACKGROUND
Patient outcomes are poor for aggressive B-cell non-Hodgkin's lymphomas not responding to or progressing within 12 months after first-line therapy. Tisagenlecleucel is an anti-CD19 chimeric antigen receptor T-cell therapy approved for diffuse large B-cell lymphoma after at least two treatment lines.
METHODS
We conducted an international phase 3 trial involving patients with aggressive lymphoma that was refractory to or progressing within 12 months after first-line therapy. Patients were randomly assigned to receive tisagenlecleucel with optional bridging therapy (tisagenlecleucel group) or salvage chemotherapy and autologous hematopoietic stem-cell transplantation (HSCT) (standard-care group). The primary end point was event-free survival, defined as the time from randomization to stable or progressive disease at or after the week 12 assessment or death. Crossover to receive tisagenlecleucel was allowed if a defined event occurred at or after the week 12 assessment. Other end points included response and safety.
RESULTS
A total of 322 patients underwent randomization. At baseline, the percentage of patients with high-grade lymphomas was higher in the tisagenlecleucel group than in the standard-care group (24.1% vs. 16.9%), as was the percentage with an International Prognostic Index score (range, 0 to 5, with higher scores indicating a worse prognosis) of 2 or higher (65.4% vs. 57.5%). A total of 95.7% of the patients in the tisagenlecleucel group received tisagenlecleucel; 32.5% of the patients in the standard-care group received autologous HSCT. The median time from leukapheresis to tisagenlecleucel infusion was 52 days. A total of 25.9% of the patients in the tisagenlecleucel group had lymphoma progression at week 6, as compared with 13.8% of those in the standard-care group. The median event-free survival in both groups was 3.0 months (hazard ratio for event or death in the tisagenlecleucel group, 1.07; 95% confidence interval, 0.82 to 1.40; P = 0.61). A response occurred in 46.3% of the patients in the tisagenlecleucel group and in 42.5% in the standard-care group. Ten patients in the tisagenlecleucel group and 13 in the standard-care group died from adverse events.
CONCLUSIONS
Tisagenlecleucel was not superior to standard salvage therapy in this trial. Additional studies are needed to assess which patients may obtain the most benefit from each approach. (Funded by Novartis; BELINDA ClinicalTrials.gov number, NCT03570892.).
论文信息
- 作者
- Bishop MR、Dickinson M、Purtill D、Barba P、Santoro A、Hamad N、Kato K、Sureda A
- 单位
- From the David and Etta Jonas Center for Cellular Therapy, University of Chicago, Chicago (M.R.B.); Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC (M. Dickinson), Fiona Stanley Hospital, Murdoch, WA (D.P.), and the Department of Haematology, St. Vincent's Hospital Sydney, and St. Vincent's Clinical School, University of New South Wales, Sydney (N.H.) - all in Australia; Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona (P. Barba) and the Clinical Hematology Department, Institut Català d'Oncologia-Hospitalet de Llobregat (A. Sureda), Barcelona, and the Hematology Department, Hospital 12 de Octubre, Complutense University, Instituto de Investigación Hospital 12 de Octubre, Centro Nacional de Investigaciones Oncológicas, Madrid (J.M.-L.) - all in Spain; the Department of Biomedical Sciences, Humanitas University and IRCCS Humanitas Research Hospital-Humanitas Cancer Center, Milan (A. Santoro); the Department of Hematology, Oncology, and Cardiovascular Medicine, Kyushu University Hospital, Fukuoka (K.K.), and Tohoku University Hospital, Sendai (H. Harigae) - both in Japan; the Third Medical Department, Paracelsus Medical University, Salzburg Cancer Research Institute-Center for Clinical Cancer and Immunology Trials and Cancer Cluster Salzburg, Salzburg (R.G.), and Internal Medicine I, Bone Marrow Transplant Unit (W.R.), and the Clinical Division of Hematology and Hemostaseology, Department of Medicine I (U.J.), Vienna General Hospital-Medical University of Vienna, Vienna - both in Austria; Assistance Publique-Hôpitaux de Paris, Hemato-Oncology, Hôpital Saint-Louis, Paris (C.T.), Centre Hospitalier Régional Universitaire de Lille, Lille (F.M.), Hospices Civils de Lyon and Université Claude Bernard Lyon 1, Lyon (E.B.), and Centre de Recherche en Cancérologie et Immunologie Nantes-Angers, INSERM, and Nantes Medical University, Nantes (S.L.G.) - all in France; the Department of Hematology, Oncology, and Tumorimmunology, Charité-University Hospital Berlin, Campus Benjamin Franklin, and the Experimental and Clinical Research Center of the Max Delbrück Center for Molecular Medicine and Charité Berlin, Berlin (M.J.), Medizinische Klinik III, LMU Klinikum, Munich (M. Dreyling), and Clinic I for Internal Medicine, University Hospital Cologne, Cologne (P. Borchmann) - all in Germany; Sarah Cannon Research Institute-Tennessee Oncology, Nashville (I.F., P.M.); the Department of Medicine, Queen Mary Hospital, Hong Kong (Y.-L.K.); the Department of Hematology, Amsterdam UMC, University of Amsterdam, Amsterdam (M.J.K.), and Universitair Medisch Centrum Utrecht, Department of Medical Oncology, Utrecht (M.C.M.) - both in the Netherlands; the Department of Oncology, Oslo University Hospital, and K.G. Jebsen Center for B-Cell Malignancies - both in Oslo (H. Holte); the National University Cancer Institute Singapore, Singapore (E.H.L.C.); the Department of Medical Oncology and Hematology, University Hospital, Zurich (A.M.S.M.), and Novartis Pharma, Basel (S.N., E.D., G.A.) - both in Switzerland; the Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health and Science University, Portland (R.T.M.); the Division of Hematologic Malignancies and Cellular Therapeutics, University of Kansas Cancer Center, Westwood (J.P.M.); Ohio State University, Columbus (D.B.); Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco (C.A.); the Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Program, Mayo Clinic, Jacksonville, FL (M.K.-D.); Novartis Pharmaceuticals, East Hanover, NJ (R.A., C.C., A.M.); the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (S.J.S.); and the Department of Lymphoma and Myeloma, M.D. Anderson Cancer Center, Houston (J.R.W.).United States
- 文献类型
- III 期临床试验 · 对照研究 · 多中心研究 · 随机对照试验 · 非美国政府资助研究
- 期刊
- The New England journal of medicine2022 Feb 17
- 原文标识
- PubMed 34904798 · DOI 10.1056/NEJMoa2116596