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
英文原题:Absolute lymphocyte count after BCMA CAR-T therapy is a predictor of response and outcomes in relapsed multiple myeloma.
Absolute lymphocyte count after BCMA CAR-T therapy is a predictor of response and outcomes in relapsed multiple myeloma.
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靶向 B 细胞成熟抗原(BCMA)的CAR-T 细胞正迅速成为多发性骨髓瘤(MM)复发/难治性(R/R)疾病治疗的重要手段。输注后 CAR-T 扩增情况已被证明与缓解深度和持续时间(DoR)有关,但对该过程的测量仍处于研究阶段。本多中心研究描述了 156 例接受 BCMA 靶向药物西达基奥仑赛或伊德卡布他仑赛治疗的复发 MM 患者,在 CAR-T 输注后前 15 天绝对淋巴细胞计数(ALC)的动态变化及其预后影响。ALC 最大值(ALCmax)较高的患者缓解更深、无进展生存期(PFS)更长、DoR 更久。ALCmax >1.0×10³/L 的患者 PFS 优于 ALCmax 不高于该水平者(30.5 个月对 6 个月;P < .001);而 ALCmax <0.5×10³/L 的患者属于高危人群,疾病早期进展且 PFS 短(风险比 3.4;95% 置信区间 2–5.8;P < .001)。多变量分析中,在校正国际分期、年龄、CAR-T 产品、高危细胞遗传学异常和既往治疗线数后,ALCmax >1.0×10³/L 及非旁骨骼髓外病变是 PFS 和 DoR 的唯一独立预测因素。
此外,流式细胞术数据提示 ALC 可作为 BCMA CAR-T 扩增的替代指标,是一种易于获取的预后标志物。据我们所知,本研究首次报告 BCMA CAR-T 输注后 ALC 与临床结局的关联及其预测 R/R MM 患者治疗反应的价值。
B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor T cells (CAR-Ts) used in multiple myeloma (MM) are rapidly becoming a mainstay in the treatment of relapsed/refractory (R/R) disease, and CAR-T expansion after infusion has been shown to inform depth and duration of response (DoR), but measuring this process remains investigational. This multicenter study describes the kinetics and prognostic impact of absolute lymphocyte count (ALC) in the first 15 days after CAR-T infusion in 156 patients with relapsed MM treated with the BCMA-targeting agents ciltacabtagene autoleucel and idecabtagene vicleucel.
Patients with higher maximum ALC (ALCmax) had better depth of response, progression-free survival (PFS), and DoR. Patients with ALCmax >1. 0 103/ L had a superior PFS (30. 5 months vs 6 months; P < . 001) compared with those with 1. 0 103/ L, whereas patients with ALCmax 0. 5 103/ L represent a high-risk group with early disease progression and short PFS (hazard ratio, 3.
4; 95% confidence interval, 2-5. 8; P < . 001). In multivariate analysis, ALCmax >1. 0 103/ L and nonparaskeletal extramedullary disease were the only independent predictors of PFS and DoR after accounting for international staging systemic staging, age, CAR-T product, high-risk cytogenetics, and the number of previous lines.
Moreover, our flow cytometry data suggest that ALC is a surrogate for BCMA CAR-T expansion and can be used as an accessible prognostic marker.
We report, to our knowledge, for the first time the association of ALC after BCMA CAR-T infusion with clinical outcomes and its utility in predicting response in patients with R/R MM.
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