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CAR-T 细胞治疗后的细胞动力学与复发/难治性骨髓瘤的缓解和毒性相关

英文原题:Cellular dynamics following CAR T cell therapy are associated with response and toxicity in relapsed/refractory myeloma.

查看英文原题

Cellular dynamics following CAR T cell therapy are associated with response and toxicity in relapsed/refractory myeloma.

PubMed 2024/01/06(内容时间) Leukemia Q1 · IF 8.8(JCR 2025)

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中文摘要

靶向B细胞成熟抗原(BCMA)的嵌合抗原受体(CAR)T细胞彻底改变了复发/难治性多发性骨髓瘤(RRMM)的治疗。然而,关于细胞(CAR)T细胞动力学及其与缓解、耐药或细胞因子释放综合征(CRS)发生之间关联的数据有限。

因此,我们对27例接受Idecabtagene vicleucel(Ide-cel)治疗的RRMM患者进行了全面的流式细胞术分析,以评估靶向BCMA的CAR-T 细胞的扩增能力、持久性及其对旁观者细胞的影响。

此外,我们还探讨了副作用,如细胞因子释放综合征(CRS)和血细胞减少。我们的结果表明,CD8+ CAR-T 细胞的体内扩增与缓解相关,然而持久性对于RRMM患者的持久缓解并非必需。

此外,我们的数据提供证据表明,在白细胞采集日CD8+ T细胞比例增加,结合成功的淋巴细胞清除,可对结局产生积极影响。我们表明,具有较高级别CRS风险的患者在淋巴细胞清除之前即可被识别。

我们广泛的表征有助于更好地理解靶向BCMA的CAR-T 细胞的动力学和效应,从而预测个体患者的缓解情况以及副作用,以便在早期阶段进行干预甚至预防。

展开英文摘要原文

B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T cells revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM).

However, data on cellular (CAR) T cell dynamics and the association with response, resistance or the occurrence of cytokine release syndrome (CRS) are limited.

Therefore, we performed a comprehensive flow cytometry analysis of 27 RRMM patients treated with Idecabtagene vicleucel (Ide-cel) to assess the expansion capacity, persistence and effects on bystander cells of BCMA-targeting CAR T cells.

Additionally, we addressed side effects, like cytokine release syndrome (CRS) and cytopenia.

Our results show that in vivo expansion of CD8 + CAR T cells is correlated to response, however persistence is not essential for durable remission in RRMM patients.

In addition, our data provide evidence, that an increased fraction of CD8 + T cells at day of leukapheresis in combination with successful lymphodepletion positively influence the outcome.

We show that patients at risk for higher-grade CRS can be identified already prior to lymphodepletion.

Our extensive characterization contributes to a better understanding of the dynamics and effects of BCMA-targeting CAR T cells, in order to predict the response of individual patients as well as side effects, which can be counteracted at an early stage or even prevented.

论文信息

作者
Fischer L、Grieb N、Born P、Weiss R、Seiffert S、Boldt A、Fricke S、Franz P
第一作者单位
Department of Hematology, Hemostaseology, Cellular Therapy and Infectiology, University Hospital of Leipzig, Leipzig, Germany.Germany
通讯作者单位
Department of Hematology, Hemostaseology, Cellular Therapy and Infectiology, University Hospital of Leipzig, Leipzig, Germany. maximilian.merz@medizin.uni-leipzig.de.Germany
文献类型
非美国政府资助研究
期刊
Leukemia2024 Feb
原文标识
PubMed 38184754 · DOI 10.1038/s41375-023-02129-y