Freeman Ciara L, Noble Jerald, Menges Meghan, Villanueva Ricardo, Nakashima Justyn Y, Figura Nicholas B, Tonseth Rolf Petter, Werner Idiaquez Dietrich, Skelson Lawrence, Smith Eric, Abraham-Miranda Julieta, Corallo Salvatore, De Avila Gabriel, Castaneda Puglianini Omar A, Liu Hien, Alsina Melissa, Nishihori Taiga, Shain Kenneth H, Baz Rachid, Blue Brandon, Grajales-Cruz Ariel, Koomen John M, Atkins Reginald M, Hansen Doris K, S Silva Ariosto, Kim Jongphil, Balagurunathan Yoganand, Locke Frederick L
Department of Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL.
Department of Clinical Science, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL.
Blood. 2025 Apr 10;145(15):1645-1657. doi: 10.1182/blood.2024024965.
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 β2 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.
嵌合抗原受体T细胞（CAR-T）疗法已成为复发难治性多发性骨髓瘤（RRMM）的突破性治疗方法。然而，这些产品的给药过程复杂，现在有了替代选择。识别能够预测治疗结果的生物标志物对于优化患者选择至关重要。目前缺乏关于RRMM患者接受CAR-T治疗时基线血清可溶性B细胞成熟抗原（sBCMA）水平和代谢肿瘤体积（MTV）效用评估的数据。我们确定了一组183例有可用血清以测量sBCMA和/或治疗前MTV的患者，这些数据来自按照标准治疗进行的正电子发射断层扫描 - 计算机断层扫描。不出所料，治疗前sBCMA的高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）以及炎症相关，并且对CAR-T相关毒性和较差的无进展生存期（PFS）具有高度预后价值。高MTV值也与较短的PFS和较差的总生存期相关。这两项指标之间观察到的低相关性促使对结果不一致的患者进行评估，发现sBCMA低而MTV高的患者浆细胞上BCMA表达通常较低/缺失且反应欠佳。我们的研究结果强调了sBCMA和MTV在为符合BCMA导向CAR-T治疗的RRMM患者制定更个性化治疗策略方面的潜在效用。
