文章：

EMN02/HOVON 95 MM试验中符合移植条件的多发性骨髓瘤患者通过多参数流式细胞术进行微小残留病评估

Minimal residual disease assessment by multiparameter flow cytometry in transplant-eligible myeloma in the EMN02/HOVON 95 MM trial

原文发布日期：2021-06-03

DOI: 10.1038/s41408-021-00498-0

类型: Article

开放获取: 是

英文摘要：

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.
 

摘要翻译： 

通过多参数流式细胞术检测的微小残留病是定义多发性骨髓瘤深度缓解的最有效工具。我们在EMN02/HO95多发性骨髓瘤III期试验中对新诊断患者开展了微小残留病相关性研究，这些患者在维持治疗前及维持治疗期间每6个月达到疑似完全缓解。患者接受大剂量美法仑或硼替佐米-美法仑-泼尼松强化治疗，随后接受硼替佐米-来那度胺-地塞米松巩固治疗或不予巩固治疗，并进行来那度胺维持治疗。骨髓样本由三家欧洲实验室按照EuroFlow流式方案进行处理，采用八色双管检测，灵敏度达10^-4-10^-5。入组微小残留病研究时，76%的患者实现微小残留病阴性。在意向治疗分析中，中位随访75个月后，微小残留病阴性患者的5年无进展生存率为66%，阳性患者为31%；5年总生存率分别为86%和69%。微小残留病阴性状态与所有亚组的疾病进展或死亡风险降低相关。在维持治疗1年时，42%的维持治疗前微小残留病阳性患者经来那度胺治疗后转为阴性。结论表明，流式细胞术检测的微小残留病是重要预后因素，来那度胺维持治疗可进一步提升微小残留病阴性率。

原文链接：

Minimal residual disease assessment by multiparameter flow cytometry in transplant-eligible myeloma in the EMN02/HOVON 95 MM trial