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血清质谱用于接受 ARI0002h CAR-T 细胞治疗的多发性骨髓瘤患者的治疗监测

英文原题:Serum mass spectrometry for treatment monitoring in patients with multiple myeloma receiving ARI0002h CAR T-cells.

查看英文原题

Serum mass spectrometry for treatment monitoring in patients with multiple myeloma receiving ARI0002h CAR T-cells.

PubMed 2024/06/18(内容时间) Br J Haematol Q2 · IF 3.6(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)T 细胞疗法提高了复发/难治性多发性骨髓瘤(RRMM)患者的疗效,其中标准电泳技术无法检测到 M 蛋白。定量免疫沉淀质谱(QIP-MS)可高灵敏度、准确测量血清 M 蛋白,并识别治疗性单克隆抗体造成的干扰。

本研究调查 QIP-MS 在 33 例接受学术界开发的 BCMA 靶向 CAR-T 细胞疗法 ARI0002h(Cesnicabtagene Autoleucel)患者中的检测结果。QIP-MS 比血清免疫固定(sIFE)提供更详细信息,能够识别糖基化 M 蛋白和少量额外峰;此外,还成功检测到达雷妥尤单抗或托珠单抗治疗可能造成的干扰。在 ARI0002h 给药后的患者监测中比较不同检测平台时,QIP-MS 与 sIFE 的总体一致率较高(78.8%),而与基于骨髓的下一代流式细胞术(NGF)的一致率仅为中等(55.6%)。

此外,在不同检测时间点,QIP-MS 的阴性率始终最低(第 1 个月和第 12 个月分别为 27.3% 和 60.0%)。QIP-MS 阳性/骨髓 NGF 阴性患者的中位 PFS 短于两种检测均阴性的患者,但差异未达到统计学显著性。

总之,据我们所知,本研究首次显示,评估 MM 患者 CAR-T 细胞治疗后的反应时,QIP-MS 作为无创检测技术可能特别有用。

展开英文摘要原文

Chimeric antigen receptor (CAR) T-cell therapies have increased the patients with relapsed/refractory multiple myeloma (RRMM) in whom standard electrophoretic techniques fail to detect the M-protein. Quantitative immunoprecipitation mass spectrometry (QIP-MS) can accurately measure serum M-protein with high sensitivity, and identify interferences caused by therapeutic monoclonal antibodies.

Here, we investigate the outcome of QIP-MS in 33 patients treated with the academic BCMA-directed CAR T-cell ARI0002h (Cesnicabtagene Autoleucel). QIP-MS offered more detailed insights than serum immunofixation (sIFE), identifying glycosylated M-proteins and minor additional peaks.

Moreover, the potential interferences owing to daratumumab or tocilizumab treatments were successfully detected. When analysing different assay platforms during patient's monitoring after ARI0002h administration, we observed that QIP-MS showed a high global concordance (78. 8%) with sIFE, whereas it was only moderate (55. 6%) with bone marrow (BM)-based next-generation flow cytometry (NGF).

Furthermore, QIP-MS consistently demonstrated the lowest negativity rate across the different timepoints (27. 3% vs. 60. 0% in months 1 and 12, respectively). Patients with QIP-MS(+)/BM-based NGF(-) showed a non-significant shorter median progression free survival than those with QIP-MS(-)/BM-based NGF(-). In summary, we show the first experience to our knowledge demonstrating that QIP-MS could be particularly useful as a non-invasive technique when evaluating response after CAR T-cell treatment in MM.

论文信息

作者
Ortiz de Landazuri I、Oliver-Caldés A、Español-Rego M、Agulló C、Contreras MT、Zabaleta A、Puig N、Cabañas V
单位
Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.Spain
期刊
British journal of haematology2024 Oct
原文标识
PubMed 38894496 · DOI 10.1111/bjh.19589