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通过质谱分析和新一代流式细胞术检测可测量残留病以评估骨髓瘤的治疗反应

Measurable residual disease by mass spectrometry and next-generation flow to assess treatment response in myeloma.

作者信息

Puig Noemí, Agulló Cristina, Contreras Teresa, Cedena María-Teresa, Martínez-López Joaquín, Oriol Albert, Blanchard María-Jesús, Ríos Rafael, Íñigo María-Belén, Sureda Anna, Lakhwani Sunil, de la Rubia Javier, González-Calle Verónica, Cabañas Valentín, Palomera Luis, Moraleda José-María, Bargay Joan, Castro Sergio, Rosiñol Laura, Bladé Joan, San-Miguel Jesús F, Lahuerta Juan-José, Paiva Bruno, Mateos María-Victoria

机构信息

Hematology Department, IBSAL, Instituto de Biología Molecular y Celular del Cáncer-Consejo Superior de Investigaciones Científicas, Centro de Investigación Biomédica en Red de Cáncer, Hospital Universitario de Salamanca, Salamanca, Spain.

Clinical Biochemistry Department, Hospital Universitario de Salamanca, Salamanca, Spain.

出版信息

Blood. 2024 Dec 5;144(23):2432-2438. doi: 10.1182/blood.2024024995.

DOI:10.1182/blood.2024024995
PMID:39293025
Abstract

Quantitative immunoprecipitation mass spectrometry (QIP-MS) allows the identification of the M-protein in patients with multiple myeloma (MM) otherwise in complete response, and could be considered suitable for measurable residual disease (MRD) evaluation in peripheral blood. In the context of the GEM2012MENOS65 and GEM2014MAIN trials, we compared the performance of QIP-MS in serum with next-generation flow (NGF) cytometry in bone marrow to assess MRD in paired samples obtained postinduction, transplant, consolidation and after 24 cycles of maintenance. At each time point, both NGF and QIP-MS were able to segregate 2 groups of patients with significantly different progression-free survival; when the evolution of the results obtained with either method was considered, maintaining or converting to MRD negativity was associated with longer survival, significantly better when compared with sustaining or converting to MRD positivity. Reemergence of MRD by QIP-MS was associated with high risk of imminent clinical progression. In conclusion, MRD evaluation by NGF and MS achieves similar prognostic value based in single time point assessments and kinetics. Thus, the minimally invasive nature of MRD monitoring by MS represents a breakthrough in highly sensitive response assessment in MM. The trials were registered at www.clinicaltrials.gov as #NCT01916252 (GEM2012MENOS65) and at EudraCT as #2012-005683-10; and as #NCT02406144 (GEM2014MAIN) and at EudraCT as 2014-00055410.

摘要

定量免疫沉淀质谱法(QIP-MS)能够鉴定处于完全缓解状态的多发性骨髓瘤(MM)患者体内的M蛋白,可被视为适用于外周血中可测量残留病(MRD)的评估。在GEM2012MENOS65和GEM2014MAIN试验的背景下,我们比较了血清中QIP-MS与骨髓中新一代流式(NGF)细胞术的性能,以评估诱导、移植、巩固及24个周期维持治疗后获取的配对样本中的MRD。在每个时间点,NGF和QIP-MS均能够区分两组无进展生存期显著不同的患者;当考虑两种方法所获结果演变情况时,维持或转变为MRD阴性与更长生存期相关,与维持或转变为MRD阳性相比显著更好。QIP-MS检测到MRD再现与即将发生临床进展的高风险相关。总之,基于单时间点评估和动力学,NGF和质谱法进行的MRD评估具有相似的预后价值。因此,质谱法监测MRD的微创特性代表了MM高敏反应评估方面的一项突破。这些试验在www.clinicaltrials.gov上注册为#NCT01916252(GEM2012MENOS6),在EudraCT上注册为#2012-005683-10;以及在www.clinicaltrials.gov上注册为#NCT024061(GEM2014MAIN),在EudraCT上注册为2014-00055410。

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引用本文的文献

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EHA-EMN Evidence-Based Guidelines for diagnosis, treatment and follow-up of patients with multiple myeloma.欧洲血液学年会-欧洲骨髓瘤网络关于多发性骨髓瘤患者诊断、治疗及随访的循证指南
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