CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
Obecabtagene autoleucel 治疗成人 B 细胞急性淋巴细胞白血病
英文原题：Obecabtagene Autoleucel in Adults with B-Cell Acute Lymphoblastic Leukemia.
查看英文原题
Obecabtagene Autoleucel in Adults with B-Cell Acute Lymphoblastic Leukemia.
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研究概要
Obe-cel 在复发/难治性 B 细胞急性淋巴细胞白血病成人患者中产生了高比例的持久缓解，且 3 级或以上免疫相关毒性反应的发生率较低。
中文摘要
奥贝卡巴他仑（obe-cel）是一种自体41BB抗CD19嵌合抗原受体（CAR）T细胞疗法，采用中等亲和力CAR，以减轻毒性并提高细胞持久性。
研究开展了一项obe-cel治疗成人（年龄≥18岁）复发/难治性B细胞急性淋巴细胞白血病（ALL）的多中心1b-2期研究。主要队列2A纳入形态学可见疾病患者；队列2B纳入可测量残留病灶患者。主要终点为队列2A总体缓解率（完全缓解或血液学恢复不完全的完全缓解）。次要终点包括无事件生存期、总生存期及安全性。
153例入组患者中，127例（83.0%）至少接受了一次obe-cel输注，并纳入疗效评估。队列2A包括94例患者，中位随访时间为20.3个月；总体缓解率为77%（95% CI：67–85），其中完全缓解率为55%（95% CI：45–66），血液学恢复不完全的完全缓解率为21%（95% CI：14–31）。预先设定的总体缓解率（≤40%）和完全缓解率（≤20%）无效假设均被拒绝（P<0.001）。至少接受一次obe-cel输注的127例患者中，中位随访时间为21.5个月；中位无事件生存期为11.9个月（95% CI：8.0–22.1），估算的6个月和12个月无事件生存率分别为65.4%和49.5%。中位总生存期为15.6个月（95% CI：12.9至无法评估），估算的6个月和12个月总生存率分别为80.3%和61.1%。2.4%的患者发生3级或以上细胞因子释放综合征，7.1%的患者发生3级或以上免疫效应细胞相关神经毒性综合征。
obe-cel使复发/难治性B细胞ALL成人患者获得较高比例的持久应答，且3级及以上免疫相关毒性发生率较低。（本研究由Autolus Therapeutics资助；FELIX试验ClinicalTrials.gov注册编号：NCT04404660。）
展开英文摘要原文
Obecabtagene autoleucel (obe-cel) is an autologous 41BB- anti-CD19 chimeric antigen receptor (CAR) T-cell therapy which uses an intermediate-affinity CAR to reduce toxic effects and improve persistence.
We conducted a phase 1b-2 multicenter study of obe-cel in adults ( 18 years of age) with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). The main cohort, cohort 2A, included patients with morphologic disease; patients in cohort 2B had measurable residual disease. The primary end point was overall remission (complete remission or complete remission with incomplete hematologic recovery) in cohort 2A. Secondary end points included event-free survival, overall survival, and safety.
Of the 153 enrolled patients, 127 (83.0%) received at least one infusion of obe-cel and were evaluable. In cohort 2A (94 patients; median follow-up, 20.3 months), overall remission occurred in 77% (95% confidence interval [CI], 67 to 85), with complete remission in 55% (95% CI, 45 to 66) and complete remission with incomplete hematologic recovery in 21% (95% CI, 14 to 31). The prespecified null hypotheses of overall remission ( 40%) and complete remission ( 20%) were rejected (P<0.001). In the 127 patients who received at least one obe-cel infusion (median follow-up, 21.5 months), the median event-free survival was 11.9 months (95% CI, 8.0 to 22.1); estimated 6- and 12-month event-free survival was 65.4% and 49.5%, respectively. The median overall survival was 15.6 months (95% CI, 12.9 to not evaluable); estimated 6- and 12-month overall survival was 80.3% and 61.1%, respectively. Grade 3 or higher cytokine release syndrome developed in 2.4% of the patients, and grade 3 or higher immune effector cell-associated neurotoxicity syndrome developed in 7.1% of the patients.
Obe-cel resulted in a high incidence of durable response among adults with relapsed or refractory B-cell ALL, with a low incidence of grade 3 or higher immune-related toxic effects. (Funded by Autolus Therapeutics; FELIX ClinicalTrials.gov number, NCT04404660.).
论文信息
- 作者
- Roddie C、Sandhu KS、Tholouli E、Logan AC、Shaughnessy P、Barba P、Ghobadi A、Guerreiro M
- 单位
- From the Cancer Institute, University College London (C.R., K.S.P., M.P.), University College London Hospitals NHS Foundation Trust (C.R.), King's College Hospital NHS Foundation Trust (D.Y.), and Autolus Therapeutics (P.L.-S., Y.Z., W.B., E.B., M.P.), London, Manchester Royal Infirmary, Manchester (E.T.), University Hospitals Birmingham NHS Foundation Trust, Birmingham (S.C.), University Hospitals Bristol NHS Foundation Trust, Bristol (K.H.), Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle (T.M.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (R.M.) - all in the United Kingdom; City of Hope National Medical Center, Duarte (K.S.S.), the Hematology, Blood and Marrow Transplant, and Cellular Therapy Program, University of California, San Francisco, San Francisco (A.C.L.), and UC Davis Medical Center, Sacramento (M.A.) - all in California; the Sarah Cannon Transplant and Cellular Therapy Program, Methodist Hospital, San Antonio (P.S.), and the University of Texas M.D. Anderson Cancer Center, Houston (E.J.) - both in Texas; Hospital Universitari Vall d'Hebron-Universitat Autónoma de Barcelona, Barcelona (P.B.), and Hospital Universitari i Politècnic La Fe, Valencia (M.G.) - both in Spain; Washington University School of Medicine, St. Louis (A.G.); the Sarah Cannon Transplant and Cellular Therapy Program, TriStar Centennial Medical Center, Nashville (J.M.P.); the University of Maryland Medical Center, Baltimore (J.A.Y.); Miller School of Medicine, University of Miami, Miami (A.M.B.), and Moffitt Cancer Center, Tampa (B.D.S.) - both in Florida; Winship Cancer Institute of Emory University, Atlanta (M.L.A.); Colorado Blood Cancer Institute, Denver (L.M.); the University of Rochester Medical Center, Rochester (K.M.O.), and Memorial Sloan Kettering Cancer Center, New York (J.H.P.) - both in New York; the David and Etta Jonas Center for Cellular Therapy, University of Chicago, Chicago (M.R.B.); and Dana-Farber Cancer Institute, Boston (D.J.D.).United Kingdom
- 文献类型
- 多中心研究 · II 期临床试验 · I 期临床试验
- 期刊
- The New England journal of medicine2024 Dec 12
- 原文标识
- PubMed 39602653 · DOI 10.1056/NEJMoa2406526
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