Background Minimal residual disease (MRD) status assessed on bone marrow aspirates is a major prognostic biomarker in multiple myeloma (MM). In this study we evaluated blood-based targeted mass spectrometry (MS-MRD) as a sensitive, minimally invasive alternative to measure MM disease activity. Methods Therapy response of 41 MM patients in the IFM-2009 clinical trial (NCT01191060) was assessed with MS-MRD on frozen sera and compared to routine state-of-the-art monoclonal protein (M-protein) diagnostics and next-generation sequencing (NGS-MRD) at 2 time points. Results In all 41 patients we were able to identify clonotypic M-protein-specific peptides and perform serum-based MS-MRD measurements. MS-MRD is significantly more sensitive to detect M-protein compared to either electrophoretic M-protein diagnostics or serum free light chain analysis. The concordance between NGS-MRD and MS-MRD status in 81 paired bone marrow/sera samples was 79%. The 50% progression-free survival (PFS) was identical (49 months) for patients who were either NGS-positive or MS-positive directly after maintenance treatment. The 50% PFS was 69 and 89 months for NGS-negative and MS-negative patients, respectively. The longest 50% PFS (96 months) was observed in patients who were MRD-negative for both methods. MS-MRD relapse during maintenance treatment was significantly correlated to poor PFS (P < 0.0001). Conclusions Our data indicate proof-of-principle that MS-MRD evaluation in blood is a feasible, patient friendly alternative to NGS-MRD assessed on bone marrow. Clinical validation of the prognostic value of MS-MRD and its complementary value in MRD-evaluation of patients with MM is warranted in an independent larger cohort.

中文翻译：

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多发性骨髓瘤微小残留疾病检测：血液中的靶向质谱与骨髓中的下一代测序

背景 对骨髓抽吸物评估的微小残留病 (MRD) 状态是多发性骨髓瘤 (MM) 的主要预后生物标志物。在这项研究中，我们评估了基于血液的靶向质谱 (MS-MRD) 作为测量 MM 疾病活动的灵敏、微创替代方法。方法 IFM-2009 临床试验 (NCT01191060) 中 41 名 MM 患者的治疗反应使用 MS-MRD 对冷冻血清进行评估，并与常规最先进的单克隆蛋白 (M-蛋白) 诊断和下一代测序进行比较(NGS-MRD) 在 2 个时间点。结果 在所有 41 名患者中，我们能够识别克隆型 M 蛋白特异性肽并进行基于血清的 MS-MRD 测量。与电泳 M 蛋白诊断或无血清轻链分析相比，MS-MRD 对检测 M 蛋白的灵敏度明显更高。在 81 对骨髓/血清样本中，NGS-MRD 和 MS-MRD 状态的一致性为 79%。对于维持治疗后直接为 NGS 阳性或 MS 阳性的患者，50% 的无进展生存期 (PFS) 相同（49 个月）。NGS 阴性和 MS 阴性患者的 50% PFS 分别为 69 个月和 89 个月。在两种方法均呈 MRD 阴性的患者中观察到最长的 50% PFS（96 个月）。维持治疗期间的 MS-MRD 复发与 PFS 差显着相关（P < 0.0001）。结论 我们的数据表明原理证明，血液中的 MS-MRD 评估是一种可行的、对患者友好的替代方法，可替代对骨髓进行评估的 NGS-MRD。