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R/R 急性淋巴细胞白血病 CAR-T 治疗中 IL-6 指导下的托珠单抗给药时机

英文原题:Timing of Tocilizumab Administration Under the Guidance of IL-6 in CAR-T Therapy for R/R Acute Lymphoblastic Leukemia.

查看英文原题

Timing of Tocilizumab Administration Under the Guidance of IL-6 in CAR-T Therapy for R/R Acute Lymphoblastic Leukemia.

PubMed 2022/06/21(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

未标注摘要:靶向CD19的CAR-T(CAR-T)细胞已使复发/难治性(R/R)急性B淋巴细胞白血病患者获得良好临床应答。

然而,细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征等严重不良事件限制了其进一步应用。托珠单抗是治疗重度CRS的基石。近年来,该药也用于治疗轻度CRS,但缺乏统计学证据明确适宜给药时机。

本研究纳入67例接受CD19-CAR-T 治疗的B-ALL患者,其中33例接受托珠单抗。依据美国移植与细胞治疗学会(ASTCT)标准,对2级CRS患者使用托珠单抗可显著缩短CRS持续时间,且不影响副作用和长期疗效。

然而,部分患者早期使用托珠单抗后仍发生重度CRS,提示引入临床实验室检测辅助用药具有重要意义。统计分析显示,IL-6水平升高不足4倍的患者接受托珠单抗后发生重度CRS的比例较高(37.5%比0%,p=0.0125),为在IL-6指导下优化CRS干预策略提供依据。临床试验注册:NCT02965092和NCT04008251(www.ClinicalTrials.gov)。

展开英文摘要原文

UNLABELLED: Chimeric antigen receptor T (CAR-T) cells targeting CD19 have achieved great clinical responses in patients with relapsed or refractory (R/R) acute B lymphoblastic leukemia.

However, severe adverse events such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome restrict it to further application. Tocilizumab is the corner stone for the treatment of severe CRS. It has been used to treat mild CRS in recent years, whereas some statistical supports clarifying the suitable timing of its administration are lacking.

Sixty-seven patients with B-cell acute lymphoblastic leukemia (B-ALL) were treated with CD19-CART and enrolled in the study, of which 33 patients received Tocilizumab. Application of Tocilizumab in patients with grade 2 CRS in American Society for Transplantation and Cellular Therapy (ASTCT) criteria can significantly shorten the duration of CRS without affecting side effects and long-term efficacy.

However, a number of patients still developed severe CRS with early use of Tocilizumab, indicating the significance of the introduction of clinical laboratories to assist medications. Statistically, patients with less than fourfold increase in IL-6 levels had a higher incidence of severe CRS after receiving Tocilizumab (37. 5% versus. 0%, p=0. 0125), which provided a basis for refining CRS intervention strategies under the guidance of IL-6. CLINICAL TRIAL REGISTRATION: www. clinicaltrials. gov, NCT02965092 and NCT04008251.

论文信息

作者
Zhang Y、Zhou F、Wu Z、Li Y、Li C、Du M、Luo W、Kou H
单位
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.China
文献类型
非美国政府资助研究
期刊
Frontiers in immunology2022
原文标识
PubMed 35799791 · DOI 10.3389/fimmu.2022.914959

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