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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
Axicabtagene Ciloleucel 作为大 B 细胞淋巴瘤的二线治疗
英文原题：Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma.
查看英文原题
Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma.
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研究概要
与标准治疗相比，Axi-cel 治疗在无事件生存期和缓解方面均有显著改善，且高级别毒性反应发生率符合预期。（由 Kite 资助；ZUMA-7 ClinicalTrials.gov 注册号：NCT03391466。）
研究思路结论见上方概要
背景
早期复发/难治性大B细胞淋巴瘤患者在接受一线化学免疫治疗后的预后较差。
方法
在这项国际性3期试验中，我们将对一线化学免疫治疗后难治或12个月内复发的大B细胞淋巴瘤患者按1:1比例随机分配，接受axicabtagene ciloleucel（axi-cel，一种自体抗CD19CAR-T 细胞疗法）或标准治疗（两或三个周期的研究者选择、方案定义的化学免疫治疗，对化学免疫治疗有应答的患者随后接受高剂量化疗联合自体干细胞移植）。主要终点为盲法中心评审的事件无进展生存期。关键次要终点为缓解和总生存期。同时评估安全性。
结果
共有180例患者被随机分配接受axi-cel治疗，179例接受标准治疗。无事件生存期的主要终点分析显示，axi-cel治疗优于标准治疗。中位随访24.9个月时，axi-cel组的中位无事件生存期为8.3个月，标准治疗组为2.0个月，24个月无事件生存率分别为41%和16%（事件或死亡的风险比为0.40；95% CI，0.31至0.51；P<0.001）。axi-cel组83%的患者出现缓解，标准治疗组为50%（完全缓解分别为65%和32%）。在一项中期分析中，axi-cel组2年估计总生存率为61%，标准治疗组为52%。接受axi-cel治疗的患者中91%发生3级或以上不良事件，接受标准治疗的患者中为83%。在接受axi-cel的患者中，6%发生3级或以上细胞因子释放综合征，21%发生3级或以上神经系统事件。未发生与细胞因子释放综合征或神经系统事件相关的死亡。
展开英文摘要原文
BACKGROUND
The prognosis of patients with early relapsed or refractory large B-cell lymphoma after the receipt of first-line chemoimmunotherapy is poor.
METHODS
In this international, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with large B-cell lymphoma that was refractory to or had relapsed no more than 12 months after first-line chemoimmunotherapy to receive axicabtagene ciloleucel (axi-cel, an autologous anti-CD19 chimeric antigen receptor T-cell therapy) or standard care (two or three cycles of investigator-selected, protocol-defined chemoimmunotherapy, followed by high-dose chemotherapy with autologous stem-cell transplantation in patients with a response to the chemoimmunotherapy). The primary end point was event-free survival according to blinded central review. Key secondary end points were response and overall survival. Safety was also assessed.
RESULTS
A total of 180 patients were randomly assigned to receive axi-cel and 179 to receive standard care. The primary end-point analysis of event-free survival showed that axi-cel therapy was superior to standard care. At a median follow-up of 24.9 months, the median event-free survival was 8.3 months in the axi-cel group and 2.0 months in the standard-care group, and the 24-month event-free survival was 41% and 16%, respectively (hazard ratio for event or death, 0.40; 95% confidence interval, 0.31 to 0.51; P<0.001). A response occurred in 83% of the patients in the axi-cel group and in 50% of those in the standard-care group (with a complete response in 65% and 32%, respectively). In an interim analysis, the estimated overall survival at 2 years was 61% in the axi-cel group and 52% in the standard-care group. Adverse events of grade 3 or higher occurred in 91% of the patients who received axi-cel and in 83% of those who received standard care. Among patients who received axi-cel, grade 3 or higher cytokine release syndrome occurred in 6% and grade 3 or higher neurologic events in 21%. No deaths related to cytokine release syndrome or neurologic events occurred.
CONCLUSIONS
Axi-cel therapy led to significant improvements, as compared with standard care, in event-free survival and response, with the expected level of high-grade toxic effects. (Funded by Kite; ZUMA-7 ClinicalTrials.gov number, NCT03391466.).
论文信息
- 作者
- Locke FL、Miklos DB、Jacobson CA、Perales MA、Kersten MJ、Oluwole OO、Ghobadi A、Rapoport AP
- 单位
- From the H. Lee Moffitt Cancer Center, Tampa, FL (F.L.L.); Stanford University School of Medicine, Stanford (D.B.M.), and Kite, a Gilead company, Santa Monica (Y.Y., S.F., J.S., M.S., C.T., P.C.) - both in California; Dana-Farber Cancer Institute, Boston (C.A.J.); Memorial Sloan Kettering Cancer Center, New York (M.-A.P.), and the University of Rochester School of Medicine, Rochester (P.M.R.) - both in New York; Amsterdam Medical Center, University of Amsterdam, Cancer Center Amsterdam, Amsterdam (M.-J.K.), University Medical Center Groningen, Groningen (T.M.), and University Medical Center Utrecht, Utrecht (M.C.M.) - all in the Netherlands; Vanderbilt-Ingram Cancer Center (O.O.O.) and Sarah Cannon Research Institute and Tennessee Oncology (I.W.F.) - both in Nashville; Washington University School of Medicine, St. Louis (A.G.); the Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore (A.P.R.); the University of Kansas Cancer Center, Kansas City (J. McGuirk); the Swedish Cancer Institute, Seattle (J.M.P.); Banner M.D. Anderson Cancer Center, Gilbert, AZ (J. Muñoz); the University of Iowa, Iowa City (U.F.); Bellvitge Institute for Biomedical Research, Universitat de Barcelona, Hematology Department, Institut Català d'Oncologia-Hospitalet, Barcelona (A.S.); University Hospitals Leuven, Leuven, Belgium (P.V.); the Division of Hematology, University of British Columbia and Leukemia-Bone Marrow Transplant Program of British Columbia, Vancouver General Hospital, BC Cancer, Vancouver, Canada (K.W.S.); Peter MacCallum Cancer Centre, Royal Melbourne Hospital and the University of Melbourne, Melbourne, VIC, Australia (M.D.); the University of Chicago Medical Center (P.A.R.) and Northwestern University Feinberg School of Medicine and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University (L.I.G.) - both in Chicago; John Theurer Cancer Center, Hackensack, NJ (L.A.L.); the Centre for Clinical Haematology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom (S.C.); and the University of Texas M.D. Anderson Cancer Center, Houston (J.R.W.).United States
- 文献类型
- III 期临床试验 · 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 34891224 · DOI 10.1056/NEJMoa2116133