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由可溶性 B 细胞成熟抗原和代谢肿瘤体积量化的肿瘤负荷决定骨髓瘤 CAR-T 结局

英文原题:Tumor burden quantified by soluble B-cell maturation antigen and metabolic tumor volume determines myeloma CAR-T outcomes.

查看英文原题

Tumor burden quantified by soluble B-cell maturation antigen and metabolic tumor volume determines myeloma CAR-T outcomes.

PubMed 2025/04/10(内容时间) Blood Q1 · IF 23.9(JCR 2025)

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中文摘要

CAR-T 细胞疗法已成为复发/难治性多发性骨髓瘤(RRMM)的突破性治疗,但产品实施复杂且目前已有替代方案。鉴定可预测治疗结局的生物标志物对于优化患者选择至关重要。RRMM患者接受CAR-T 治疗前血清可溶性B细胞成熟抗原(sBCMA)水平与代谢肿瘤体积(MTV)的联合价值研究有限。

我们确定一个包含183例患者的队列,这些患者有血清样本可测定sBCMA,和/或有按标准诊疗流程获得的正电子发射断层扫描-计算机断层扫描(PET-CT)治疗前MTV数据。与预期一致,较高的治疗前sBCMA水平与其他已确立的肿瘤负荷标志物(如骨髓浆细胞和β2微球蛋白)及炎症相关,并能高度预测CAR-T 相关毒性及无进展生存期(PFS)较差。MTV较高也与PFS缩短和总生存期较差相关。两项指标相关性较弱,因此研究者评估了结果不一致的患者,发现sBCMA低而MTV高者常有浆细胞BCMA表达低或缺失,且治疗应答欠佳。研究结果突显sBCMA和MTV可能有助于为符合BCMA靶向CAR-T 治疗条件的RRMM患者制定更加个体化的治疗策略。

展开英文摘要原文

Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a breakthrough treatment for relapsed and refractory multiple myeloma (RRMM).

However, these products are complex to deliver, and alternative options are now available. Identifying biomarkers that can predict therapeutic outcomes is crucial for optimizing patient selection. There is a paucity of data evaluating the utility of both serum soluble B-cell maturation antigen (sBCMA) levels and metabolic tumor volume (MTV) at baseline in patients with RRMM undergoing CAR-T therapy.

We identified a cohort of 183 patients with available serum to measure sBCMA and/or pretreatment MTV, derived from positron emission tomography-computed tomography scans obtained per standard of care. Expectedly, high pretreatment levels of sBCMA correlated with other established markers of tumor burden (eg, bone marrow plasma cells and 2 microglobulin) and inflammation and were highly prognostic for CAR-T-related toxicities and inferior progression-free survival (PFS).

High MTV values were also associated with shorter PFS and inferior overall survival. The poor correlation observed between these 2 measures prompted evaluation of those with discordant results, identifying that those with low sBCMA and high MTV frequently had low/absent BCMA expression on plasma cells and suboptimal response.

Our findings highlight the potential utility of sBCMA and MTV to facilitate more personalized treatment strategies in the management of RRMM eligible for BCMA-directed CAR-T.

论文信息

作者
Freeman CL、Noble J、Menges M、Villanueva R、Nakashima JY、Figura NB、Tonseth RP、Werner Idiaquez D
单位
Department of Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL.United States
期刊
Blood2025 Apr 10
原文标识
PubMed 39652773 · DOI 10.1182/blood.2024024965