文章：

循环中VCAM-1水平升高与多发性骨髓瘤患者疾病进展和不良生存相关：硼替佐米和来那度胺治疗后降低

Increased circulating VCAM-1 correlates with advanced disease and poor survival in patients with multiple myeloma: reduction by post-bortezomib and lenalidomide treatment

原文发布日期：2016-05-27

DOI: 10.1038/bcj.2016.37

类型: Original Article

开放获取: 是

英文摘要：

Circulating vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and selectins were prospectively measured in 145 newly-diagnosed patients with symptomatic myeloma (NDMM), 61 patients with asymptomatic/smoldering myeloma (SMM), 47 with monoclonal gammopathy of undetermined significance (MGUS) and 87 multiple myeloma (MM) patients at first relapse who received lenalidomide- or bortezomib-based treatment (RD, n=47; or VD, n=40). Patients with NDMM had increased VCAM-1 and ICAM-1 compared with MGUS and SMM patients. Elevated VCAM-1 correlated with ISS-3 and was independently associated with inferior overall survival (OS) (45 months for patients with VCAM-1 >median vs 75 months, P=0.001). MM patients at first relapse had increased levels of ICAM-1 and L-selectin, even compared with NDMM patients and had increased levels of VCAM-1 compared with MGUS and SMM. Both VD and RD reduced dramatically serum VCAM-1 after four cycles of therapy, but only VD reduced serum ICAM-1, irrespective of response to therapy. The reduction of VCAM-1 was more pronounced after RD than after VD. Our study provides evidence for the prognostic value of VCAM-1 in myeloma patients, suggesting that VCAM-1 could be a suitable target for the development of anti-myeloma therapies. Furthermore, the reduction of VCAM-1 and ICAM-1 by RD and VD supports the inhibitory effect of these drugs on the adhesion of MM cells to stromal cells.

摘要翻译： 

本研究前瞻性检测了145例新诊断的有症状骨髓瘤（NDMM）患者、61例无症状/冒烟型骨髓瘤（SMM）患者、47例意义未明的单克隆丙种球蛋白病（MGUS）患者以及87例首次复发并接受来那度胺或硼替佐米为基础治疗方案（RD方案47例，VD方案40例）的多发性骨髓瘤（MM）患者循环血管细胞黏附分子-1（VCAM-1）、细胞间黏附分子-1（ICAM-1）及选择素水平。与MGUS和SMM患者相比，NDMM患者的VCAM-1和ICAM-1水平升高。VCAM-1升高与国际分期系统（ISS）-3分期相关，且是总生存期缩短的独立危险因素（VCAM-1高于中位值患者总生存期为45个月 vs 75个月，P=0.001）。首次复发的MM患者即使与NDMM患者相比，其ICAM-1和L-选择素水平仍更高，且VCAM-1水平也高于MGUS和SMM患者。经四个周期治疗后，VD和RD方案均显著降低血清VCAM-1水平，但仅VD方案可降低血清ICAM-1水平（与治疗反应无关）。RD方案对VCAM-1的降低作用较VD方案更显著。本研究证实了VCAM-1在骨髓瘤患者中的预后价值，提示VCAM-1可能成为抗骨髓瘤治疗的潜在靶点。此外，RD和VD方案对VCAM-1及ICAM-1的抑制作用，支持这些药物能抑制MM细胞与基质细胞的黏附。

原文链接：

Increased circulating VCAM-1 correlates with advanced disease and poor survival in patients with multiple myeloma: reduction by post-bortezomib and lenalidomide treatment