Mailankody Sham, Korde Neha, Lesokhin Alexander M, Lendvai Nikoletta, Hassoun Hani, Stetler-Stevenson Maryalice, Landgren Ola
Multiple Myeloma Section, Lymphoid Malignancies Branch, Centre for Cancer Research, National Institutes of Health, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Myeloma Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Nat Rev Clin Oncol. 2015 May;12(5):286-95. doi: 10.1038/nrclinonc.2014.239. Epub 2015 Jan 27.
Outcomes for patients with multiple myeloma (MM) have improved substantially in the past decade, with improvements in both progression-free survival and overall survival. Many patients are now achieving a complete response to treatment, and consequently highly sensitive assays are needed for detection of minimal residual disease (MRD) in patients with MM. Results of multicolour flow cytometry and deep-sequencing studies suggest that among patients achieving a complete response, MRD-negative status is associated with significant improvements in progression-free survival and overall survival. Despite the increasing need for MRD testing in patients with MM, considerable heterogeneity in techniques for MRD detection hinders the clinical interpretation of their results. The criteria used to define MRD, strengths and weaknesses of the major types of tests (flow cytometry versus molecular testing), and the optimal sample type (bone marrow aspirate versus peripheral blood) are all unresolved dilemmas in MRD testing. This Review presents an overview of the various techniques for MRD detection in patients with MM. In addition, this article discusses challenges and opportunities for the routine use of MRD testing, possible future directions for clinical trials and implications for drug approval processes.
在过去十年中，多发性骨髓瘤（MM）患者的预后有了显著改善，无进展生存期和总生存期均有所提高。现在许多患者对治疗实现了完全缓解，因此需要高灵敏度的检测方法来检测MM患者的微小残留病（MRD）。多色流式细胞术和深度测序研究结果表明，在实现完全缓解的患者中，MRD阴性状态与无进展生存期和总生存期的显著改善相关。尽管MM患者对MRD检测的需求日益增加，但MRD检测技术存在相当大的异质性，这阻碍了对其结果的临床解读。用于定义MRD的标准、主要检测类型（流式细胞术与分子检测）的优缺点以及最佳样本类型（骨髓穿刺液与外周血）都是MRD检测中尚未解决的难题。本综述概述了MM患者MRD检测的各种技术。此外，本文还讨论了MRD检测常规应用面临的挑战和机遇、临床试验可能的未来方向以及对药物审批流程的影响。
