CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
复发/难治性多发性骨髓瘤 BCMA 靶向 CAR-T 细胞治疗后 T 细胞亚群变化、既往血细胞减少与高铁蛋白血症同血细胞减少相关：一项前瞻性综合生物标志物研究结果
英文原题：Changes in T-cell subsets, preexisting cytopenias and hyperferritinaemia correlate with cytopenias after BCMA targeted CAR T-cell therapy in relapsed/refractory multiple myeloma: Results from a prospective comprehensive biomarker study.
查看英文原题
Changes in T-cell subsets, preexisting cytopenias and hyperferritinaemia correlate with cytopenias after BCMA targeted CAR T-cell therapy in relapsed/refractory multiple myeloma: Results from a prospective comprehensive biomarker study.
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中文摘要
CAR-T 治疗复发/难治性（RR）多发性骨髓瘤（MM）后血细胞减少的生物标志物尚未完全明确。本研究前瞻性分析了 58 例接受 BCMA 靶向 CAR-T 治疗的 RRMM 患者的 275 份连续外周血样本，并按采样时间分为三组：（i）基线（白细胞单采前）；（ii）第 30 天；（iii）CAR-T 治疗后第 30 天以后。研究评估实验室数据，并用流式细胞术检测 CAR-T 细胞亚群。基线高铁蛋白血症是 CAR-T 治疗后长期 3 级贫血（r=0.47，P<0.001）和血小板减少（r=0.44，P=0.002）的危险因素。基线血红蛋白（Hb）和血小板（PLT）偏低分别与长期 3 级贫血（r=−0.56，P<0.001）及血小板减少（r=−0.44，P=0.002）相关。研究观察到 CAR-T 输注后 CAR 阴性 T 细胞亚群发生动态变化。治疗后晚期（第 30 天以后），CD4 初始 T 细胞（CD4Tn）比例与贫血相关（r=0.41，P=0.0014）；淋巴细胞减少与 CD8+ T 细胞（r=0.72，P<0.001）及 CD8 效应 T 细胞（CD8Teff，r=0.64，P<0.001）比例相关。CD4 中央记忆 T 细胞（CD4Tcm）比例与白细胞减少相关（r=−0.49，P<0.001）。
总之，治疗前存在的血细胞减少和高铁蛋白血症提示 CAR-T 后 3 级血细胞减少可能持续较久。持续性血细胞减少可能与 CAR-T 治疗后 CAR 阴性 T 细胞亚群变化导致的免疫重塑有关。
展开英文摘要原文
Biomarkers for cytopenias following CAR T-cell treatment in relapsed/refractory (RR) multiple myeloma (MM) are not completely defined.
We prospectively analysed 275 sequential peripheral blood (PB) samples from 58 RRMM patients treated with BCMA-targeted CAR T cells, and then divided them into three groups: (i) baseline (before leukapheresis), (ii) day+30, and (iii) >day+30 after CAR T-cell therapy.
We evaluated laboratory data and performed flow cytometry to determine the (CAR) T-cell subsets. Baseline hyperferritinaemia was a risk factor for long-lasting grade 3 anaemia (r = 0. 47, p < 0. 001) and thrombocytopenia (r = 0. 44, p = 0. 002) after CAR T-cell therapy. Low baseline haemoglobin (Hb) and PLT were associated with long-lasting grade 3 anaemia (r = -0. 56, p < 0. 001) and thrombocytopenia (r = -0. 44, p = 0. 002) respectively.
We observed dynamics of CAR-negative T-cell subsets following CAR T-cell infusion. In the late phase after CAR T-cell therapy (>day+30), CD4Tn frequency correlated with anaemia (r = 0. 41, p = 0. 0014) and lymphocytopenia was related to frequencies of CD8 + T cells (r = 0. 72, p < 0. 001) and CD8Teff (r = 0. 64, p < 0. 001).
CD4Tcm frequency was correlated with leucocytopenia (r = -0. 49, p < 0. 001). In summary, preexisting cytopenias and hyperferritinaemia indicated long duration of grade 3 post-CAR T-cell cytopenias. Prolonged cytopenia may be related to immune remodelling with a shift in the CAR-negative T-cell subsets following CAR T-cell therapy.
论文信息
- 作者
- Zhou X、Wagner V、Scheller L、Stanojkovska E、Riedhammer C、Xiao X、Steinhardt MJ、Vogt C
- 单位
- Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany.Germany
- 期刊
- British journal of haematology2024 Sep
- 原文标识
- PubMed 38719214 · DOI 10.1111/bjh.19515