阿基仑赛注射液二线治疗大 B 细胞淋巴瘤。

Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma.

机构信息

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.).

出版信息

N Engl J Med. 2022 Feb 17;386(7):640-654. doi: 10.1056/NEJMoa2116133. Epub 2021 Dec 11.

DOI:10.1056/NEJMoa2116133

PMID:34891224

Abstract

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.).

摘要

背景

在接受一线化疗免疫治疗后，早期复发或难治性大 B 细胞淋巴瘤患者的预后较差。

方法

在这项国际 3 期临床试验中，我们按 1:1 的比例随机分配在一线化疗免疫治疗后 12 个月内发生难治或复发的大 B 细胞淋巴瘤患者接受 axi-cel（自体抗 CD19 嵌合抗原受体 T 细胞治疗）或标准护理（接受 2 或 3 个周期的研究者选择的、方案定义的化疗免疫治疗，随后对化疗免疫治疗有反应的患者进行大剂量化疗联合自体干细胞移植）。主要终点是根据盲法中心评估的无事件生存。主要次要终点是反应和总生存。还评估了安全性。

结果

共有 180 名患者被随机分配接受 axi-cel，179 名患者接受标准护理。无事件生存的主要终点分析显示，axi-cel 治疗优于标准护理。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，标准护理组为 2.0 个月，24 个月时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%置信区间为 0.31 至 0.51；P<0.001）。axi-cel 组有 83%的患者发生应答，而标准护理组有 50%的患者发生应答（完全缓解率分别为 65%和 32%）。中期分析时，axi-cel 组的 2 年总生存率估计为 61%，标准护理组为 52%。接受 axi-cel 治疗的患者中有 91%发生 3 级或以上的不良事件，接受标准护理的患者中有 83%发生 3 级或以上的不良事件。接受 axi-cel 治疗的患者中，有 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。没有与细胞因子释放综合征或神经系统事件相关的死亡。