肿瘤细胞治疗研究
英文原题：Idecabtagene vicleucel and endogenous T-cell phenotypes linked to progression-free survival in relapsed multiple myeloma.
Idecabtagene vicleucel and endogenous T-cell phenotypes linked to progression-free survival in relapsed multiple myeloma.
输注后第 1 个月时，CAR-T 细胞 >1%、CD4/CD8 CAR-T 细胞比值 >0.09 以及非活化非细胞溶解性 CAR-T 细胞丰度更高，可识别出 PFS 更长的患者。
要实现多发性骨髓瘤（MM）免疫治疗的个体化并改善结局，需要更深入了解嵌合抗原受体（CAR）及内源性 T 细胞表型与无进展生存（PFS）的关联。我们对 KarMMa 试验中接受 idecabtagene vicleucel 治疗的 107 例 MM 患者的 258 份骨髓抽吸样本，采用多维计算流式细胞术刻画免疫动态并研究其预后价值。筛查时，PD-1⁺细胞毒性 T 细胞及 ICOS⁻TIGIT⁺调节性 T 细胞（Treg）比例升高与 PFS 延长相关。输注后第 1 个月，CAR-T 细胞比例>1%、CD4/CD8 CAR-T 比值>0.09，以及非活化、非细胞毒性 CAR-T 细胞较多，均可识别出 PFS 较长的患者。值得注意的是，CAR-T 输注后最近一次评估时，115 个内源性 T 细胞簇中有 47 个具有预后价值。ICOS⁺TIGIT⁻ Treg 比例较低与 PFS 延长的关联最强。总体而言，这项大规模动态免疫分析显示，抗 B 细胞成熟抗原（BCMA）CAR-T 治疗前单采血液成分中的 T 细胞组成，以及输注后 CAR-T 和内源性 T 细胞表型，均与 PFS 相关。这些发现有望转化至常规实验室检测，帮助深入理解 R/R MM 患者对 CAR-T 的应答和耐药。
Improved understanding of how chimeric antigen receptor (CAR) and endogenous T-cell phenotypes associate with progression-free survival (PFS) is needed to individualize and improve immunotherapy outcomes in multiple myeloma (MM). We characterized and investigated the prognostic value of immune dynamics defined with multidimensional and computational flow cytometry in 258 bone marrow aspirates from 107 MM patients treated with idecabtagene vicleucel in the KarMMa trial. At screening, there was an association between longer PFS and increased percentages of PD1 + cytotoxic T cells and ICOS - TIGIT + Tregs. At Month 1 after infusion, the presence of >1% CAR-T cells, a CD4/CD8 CAR-T-cell ratio >0.09, and greater abundance of non-activated non-cytolytic CAR-T cells identified patients with longer PFS. Notably, 47 of the 115 endogenous T-cell clusters were prognostic at the latest assessment performed after CAR-T infusion. Lower percentages of ICOS + TIGIT - Tregs showed the strongest association with longer PFS. Altogether, this large dataset of dynamic immune profiling throughout treatment with anti-B-cell maturation antigen (anti-BCMA) CAR-T cells uncovered that the T-cell composition prior to apheresis as well as CAR-T and endogenous T-cell phenotypes after infusion associates with PFS. These findings have potential for translation into routine laboratory practice for improved understanding of response and resistance to CAR-T cells in relapsed/refractory MM.
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