多发性骨髓瘤微小残留病检测的研究进展

Advances of minimal residual disease detection in patients with multiple myeloma

近年来随着新药物的临床应用,多发性骨髓瘤(multiple myeloma,MM)患者的预后有了根本性的改善,但目前仍不能达到临床治愈。主要障碍为微小残留病(minimal residual diseases,MRD)的存在,其对于患者无进展生存期(progression-free survival,PFS)和总生存期(overall survival,OS)具有重要影响。考虑到患者的克隆异质性、基因不稳定性和无效免疫监视,准确定义和精准检测MRD对制定临床治疗决策十分重要,同时MRD阴性也是患者维持治疗的理论终点和新药临床试验的重要研究终点之一。迄今为止,在检测精度、标准化和普遍适用性方面尚缺乏完美的MRD检测手段。本文综述包括流式细胞术和各种分子生物学检测方法在内的检测MM患者MRD的主要技术,对其各自的优缺点和未来发展方向予以阐述。

In the past decade, outcomes for patients with multiple myeloma（MM） have improved substantially with the clinical application of novel agents. However, the primary hurdle in the path to curing MM is minimal residual diseases（MRDs）, which play a critical role in either progression-free survival or overall survival. A better definition of MRD will aid in tailoring MM therapy further in view of the clonal heterogeneity and genomic instability, and overcome patients＇ ineffective immune surveillance. MRD analysis can define the logical endpoint for maintenance therapy; in addition, it also aids in providing better clinical endpoints for studies. However, until now,all techniques have flaws in the detection of MRD in the fields of standardization, universal availability, or proper accuracy. This review provides an overview of the advantages and disadvantages of various techniques for MRD detection in patients with MM, including flow cytometry and several molecular techniques, and discusses the direction of its future improvements.