Minimal residual disease (MRD) by multiparameter flow cytometry (MFC) is the most effective tool to define a deep response in multiple myeloma (MM). We conducted an MRD correlative study of the EMN02/HO95 MM phase III trial in newly diagnosed MM patients achieving a suspected complete response before maintenance and every 6 months during maintenance. Patients received high-dose melphalan (HDM) versus bortezomib-melphalan-prednisone (VMP) intensification, followed by bortezomib-lenalidomide-dexamethasone (VRd) versus no consolidation, and lenalidomide maintenance. Bone marrow (BM) samples were processed in three European laboratories, applying EuroFlow-based MFC protocols (eight colors, two tubes) with 10⁻⁴−10⁻⁵ sensitivity. At enrollment in the MRD correlative study, 76% (244/321) of patients were MRD-negative. In the intention-to-treat analysis, after a median follow-up of 75 months, 5-year progression-free survival was 66% in MRD-negative versus 31% in MRD-positive patients (HR 0.39; p < 0.001), 5-year overall survival was 86% versus 69%, respectively (HR 0.41; p < 0.001). MRD negativity was associated with reduced risk of progression or death in all subgroups, including ISS-III (HR 0.37) and high-risk fluorescence in situ hybridization (FISH) patients (HR 0.38;). In the 1-year maintenance MRD population, 42% of MRD-positive patients at pre-maintenance became MRD-negative after lenalidomide exposure. In conclusion, MRD by MFC is a strong prognostic factor. Lenalidomide maintenance further improved MRD-negativity rate.

多参数流式细胞术 (MFC) 检测微小残留病 (MRD) 是定义多发性骨髓瘤 (MM) 深度反应的最有效工具。我们对新诊断的 MM 患者进行了 EMN02/HO95 MM III 期试验的 MRD 相关性研究，这些患者在维持治疗前和维持治疗期间每 6 个月实现了疑似完全缓解。患者接受高剂量马法兰（HDM）与硼替佐米-马法兰-泼尼松（VMP）强化治疗，随后接受硼替佐米-来那度胺-地塞米松（VRd）与无巩固治疗，以及来那度胺维持治疗。骨髓 (BM) 样本在三个欧洲实验室进行处理，采用基于 EuroFlow 的 MFC 方案（八种颜色，两管），灵敏度为 10 ^-4 -10 ^-5。在 MRD 相关研究入组时，76% (244/321) 的患者为 MRD 阴性。在意向治疗分析中，中位随访 75 个月后，MRD 阴性患者的 5 年无进展生存率为 66%，而 MRD 阳性患者的 5 年无进展生存率为 31%（HR 0.39；p <  0.001）， 5 年总生存率分别为 86% 和 69%（HR 0.41；p  < 0.001）。MRD 阴性与所有亚组的进展或死亡风险降低相关，包括 ISS-III (HR 0.37) 和高风险荧光原位杂交 (FISH) 患者 (HR 0.38;)。在 1 年维持 MRD 人群中，维持前 MRD 阳性患者中有 42% 在来那度胺暴露后变为 MRD 阴性。总之，MFC 的 MRD 是一个强有力的预后因素。来那度胺维持治疗进一步改善了 MRD 阴性率。