Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Cancer Med. 2024 Jul;13(14):e70019. doi: 10.1002/cam4.70019.
Multiple myeloma (MM) is an incurable B-cell malignancy often accompanied by profound immunodeficiency. Lenalidomide (Len) is an immunomodulatory drug that exerts promising therapeutic effects on MM through the immune system. However, predictive markers related to the effects of Len treatment are not fully understood. This study aimed to identify candidate biomarkers for predicting the clinical efficacy of Len and dexamethasone (Ld) therapy through a comprehensive analysis of serum cytokines. The levels of 48 cytokines in the serum of patients with MM just before Ld therapy (n = 77), at the time of best response (n = 56), and at disease progression (n = 49) were measured and evaluated. Patients with high IL-18 and M-CSF levels showed significantly shorter progression-free survival and overall survival (OS). In contrast, patients with high PDGF-BB levels had longer survival. Moreover, low levels of G-CSF, IL-7, IL-8, and SDF-1α were associated with shorter OS after Ld therapy. During Ld therapy, pro-inflammatory cytokines such as IL-2Rα, IL-18, and TNF-α were decreased, while IFN-γ was increased. IL-4 and IL-6 levels increased during disease progression. In conclusion, this study provides a better understanding of the association between cytokines and the efficacy of Ld therapy as well as the unique changes in cytokines related to inflammatory and immune responses during Ld therapy.
多发性骨髓瘤(MM)是一种不可治愈的 B 细胞恶性肿瘤,常伴有严重的免疫缺陷。来那度胺(Len)是一种免疫调节药物,通过免疫系统对 MM 发挥有前途的治疗作用。然而,与 Len 治疗效果相关的预测标志物尚未完全了解。本研究旨在通过对血清细胞因子的综合分析,确定预测 Len 和地塞米松(Ld)治疗临床疗效的候选生物标志物。在 Ld 治疗前(n=77)、最佳反应时(n=56)和疾病进展时(n=49)测量并评估了 77 例 MM 患者血清中 48 种细胞因子的水平。IL-18 和 M-CSF 水平高的患者无进展生存期和总生存期(OS)明显缩短。相比之下,PDGF-BB 水平高的患者生存时间更长。此外,G-CSF、IL-7、IL-8 和 SDF-1α 水平低与 Ld 治疗后 OS 缩短相关。在 Ld 治疗期间,促炎细胞因子如 IL-2Rα、IL-18 和 TNF-α 降低,而 IFN-γ 增加。在疾病进展期间,IL-4 和 IL-6 水平升高。总之,本研究更好地了解了细胞因子与 Ld 治疗疗效之间的关系,以及与 Ld 治疗期间炎症和免疫反应相关的细胞因子的独特变化。