Obecabtagene Autoleucel in Adults with B-Cell Acute Lymphoblastic Leukemia.

IF 96.2 1区 医学 Q1 MEDICINE, GENERAL & INTERNAL
New England Journal of Medicine Pub Date : 2024-12-12 Epub Date: 2024-11-27 DOI:10.1056/NEJMoa2406526
Claire Roddie, Karamjeet S Sandhu, Eleni Tholouli, Aaron C Logan, Paul Shaughnessy, Pere Barba, Armin Ghobadi, Manuel Guerreiro, Deborah Yallop, Mehrdad Abedi, Jeremy M Pantin, Jean A Yared, Amer M Beitinjaneh, Sridhar Chaganti, Katharine Hodby, Tobias Menne, Martha L Arellano, Ram Malladi, Bijal D Shah, Luke Mountjoy, Kristen M O'Dwyer, Karl S Peggs, Pierre Lao-Sirieix, Yiyun Zhang, Wolfram Brugger, Edgar Braendle, Martin Pule, Michael R Bishop, Daniel J DeAngelo, Jae H Park, Elias Jabbour
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引用次数: 0

Abstract

Background: Obecabtagene autoleucel (obe-cel) is an autologous 41BB-ζ anti-CD19 chimeric antigen receptor (CAR) T-cell therapy which uses an intermediate-affinity CAR to reduce toxic effects and improve persistence.

Methods: 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.

Results: 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.

Conclusions: 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.).

用于 B 细胞急性淋巴细胞白血病成人患者的 Obecabtagene Autoleucel。
背景:Obecabtagene autoleucel(obe-cel)是一种自体41BB-ζ抗CD19嵌合抗原受体(CAR)T细胞疗法,它使用中间亲和力CAR来减少毒性作用并提高持久性:我们对复发或难治性B细胞急性淋巴细胞白血病(ALL)成人患者(≥18岁)进行了obe-cel的1b-2期多中心研究。主要队列(队列 2A)包括患有形态学疾病的患者;队列 2B 中的患者患有可测量的残留疾病。主要终点是2A组患者的总体缓解(完全缓解或完全缓解伴不完全血液学恢复)。次要终点包括无事件生存期、总生存期和安全性:在 153 名入组患者中,127 人(83.0%)至少接受了一次 obe-cel 输注,并进行了评估。在队列 2A(94 例患者;中位随访 20.3 个月)中,77% 的患者(95% 置信区间 [CI],67-85)获得了总体缓解,55% 的患者(95% 置信区间,45-66)获得了完全缓解,21% 的患者(95% 置信区间,14-31)获得了完全缓解但血液学功能未完全恢复。总体缓解率(≤40%)和完全缓解率(≤20%)的预设零假设被拒绝(PConclusions:在复发或难治性B细胞ALL成人患者中,Obe-cel的持久应答发生率高,3级或更高免疫相关毒性反应发生率低。(由 Autolus Therapeutics 资助);FELIX ClinicalTrials.gov 编号:NCT04404660)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
New England Journal of Medicine
New England Journal of Medicine 医学-医学:内科
CiteScore
145.40
自引率
0.60%
发文量
1839
审稿时长
1 months
期刊介绍: The New England Journal of Medicine (NEJM) stands as the foremost medical journal and website worldwide. With an impressive history spanning over two centuries, NEJM boasts a consistent publication of superb, peer-reviewed research and engaging clinical content. Our primary objective revolves around delivering high-caliber information and findings at the juncture of biomedical science and clinical practice. We strive to present this knowledge in formats that are not only comprehensible but also hold practical value, effectively influencing healthcare practices and ultimately enhancing patient outcomes.
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