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 pre-treatment MTV, derived from positron emission tomography-computed tomography (PET-CT) scans obtained per standard of care. Expectedly, high pre-treatment levels of sBCMA correlated with other established markers of tumor burden (e.g., bone marrow plasma cells/BMPCs, beta2 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 (OS). The poor correlation observed between these two 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.

中文翻译：

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通过可溶性 B 细胞成熟抗原和代谢肿瘤体积量化的肿瘤负荷决定了骨髓瘤 CAR-T 结果。


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，这些产品的交付很复杂，现在有其他选择。识别可以预测治疗结果的生物标志物对于优化患者选择至关重要。缺乏评估接受 CAR-T 治疗的 RRMM 患者基线时血清可溶性 B 细胞成熟抗原 （sBCMA） 水平和代谢肿瘤体积 （MTV） 效用的数据。我们确定了一组 183 名患者，这些患者有可用的血清来测量 sBCMA 和/或治疗前 MTV，这些血清来自根据护理标准获得的正电子发射断层扫描-计算机断层扫描 （PET-CT）。预期，sBCMA 的高治疗前水平与其他已确定的肿瘤负荷标志物 （例如，骨髓浆细胞/BMPCs、β2 微球蛋白） 和炎症相关，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。高 MTV 值也与较短的 PFS 和较差的总生存期 （OS） 相关。在这两种测量之间观察到的不良相关性促使对结果不一致的患者进行评估，确定低 sBCMA 和高 MTV 的患者经常在浆细胞上出现低/不存在 BCMA 表达和次优反应。我们的研究结果强调了 sBCMA 和 MTV 的潜在效用，以促进在符合BCMA定向CAR-T条件的RRMM管理中制定更加个性化的治疗策略。