Purpose: M-protein is a well-established biomarker used for multiple myeloma monitoring. Current improvements in multiple myeloma treatment created the need to monitor minimal residual disease (MRD) with high sensitivity. Measuring residual levels of M-protein in serum by MS was established as a sensitive assay for disease monitoring. In this study we evaluated the performance of EasyM—a noninvasive, sensitive, MS-based assay for M-protein monitoring. Experimental Design: Twenty-six patients enrolled in MCRN-001 clinical trial of two high-dose alkylating agents as conditioning followed by lenalidomide maintenance were selected for the study. All selected patients achieved complete responses (CR) during treatment, whereas five experienced progressive disease on study. The M-protein of each patient was first sequenced from the diagnostic serum using our de novo protein sequencing platform. The patient-specific M-protein peptides were then measured by targeted MS assay to monitor the response to treatment. Results: The M-protein doubling over 6 months measured by EasyM could predict the relapse in 4 of 5 relapsed patients 2 to 11 months earlier than conventional testing. In 21 disease-free patients, the M-protein was still detectable by EasyM despite normal FLC and MRD negativity. Importantly, of 72 MRD negative samples with CR status, 62 were positive by EasyM. The best sensitivity achieved by EasyM, detecting 0.58 mg/L of M-protein, was 1,000- and 200-fold higher compared with serum protein electrophoresis and immunofixation electrophoresis, respectively. Conclusions: EasyM was demonstrated to be a noninvasive, sensitive assay with superior performance compared with other assays, making it ideal for multiple myeloma monitoring and relapse prediction. This article is featured in Highlights of This Issue, [p. 4945][1] [1]: /lookup/volpage/27/4945?iss=18

中文翻译：

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一种基于质谱的个性化检测方法，用于监测多发性骨髓瘤患者的 M 蛋白 (EasyM)

目的：M 蛋白是一种成熟的生物标志物，用于监测多发性骨髓瘤。当前多发性骨髓瘤治疗的改进需要以高灵敏度监测微小残留病 (MRD)。通过 MS 测量血清中 M 蛋白的残留水平被确立为疾病监测的灵敏测定。在这项研究中，我们评估了 EasyM 的性能——一种用于 M 蛋白监测的无创、灵敏、基于 MS 的检测方法。实验设计：26 名参加 MCRN-001 临床试验的患者选择了两种高剂量烷化剂作为调节剂，然后进行来那度胺维持。所有选定的患者在治疗期间均获得完全缓解 (CR)，而五名患者在研究中经历了疾病进展。每个患者的 M 蛋白首先使用我们的从头蛋白测序平台从诊断血清中测序。然后通过靶向 MS 测定法测量患者特异性 M 蛋白肽，以监测对治疗的反应。结果：通过 EasyM 测量的超过 6 个月的 M 蛋白倍增可以预测 5 名复发患者中 4 名的复发，比常规测试提前 2 至 11 个月。在 21 名无病患者中，尽管 FLC 和 MRD 阴性，但 EasyM 仍可检测到 M 蛋白。重要的是，在 72 个具有 CR 状态的 MRD 阴性样本中，62 个通过 EasyM 呈阳性。与血清蛋白电泳和免疫固定电泳相比，EasyM 实现的最佳灵敏度（检测 0.58 mg/L 的 M 蛋白）分别高 1,000 倍和 200 倍。结论：EasyM 被证明是一种无创、与其他检测方法相比具有卓越性能的灵敏检测方法，使其成为多发性骨髓瘤监测和复发预测的理想选择。这篇文章刊登在本期要闻中，[p。4945][1][1]:/lookup/volpage/27/4945?iss=18