The significance of free light-chain ratio in light-chain monoclonal gammopathy of undetermined significance: a flow cytometry sub-study of the iStopMM screening study

IF 12.9 1区医学 Q1 HEMATOLOGY Blood Cancer Journal Pub Date : 2024-12-18 DOI:10.1038/s41408-024-01201-9

Jón Þórir Óskarsson, Sæmundur Rögnvaldsson, Sigrun Thorsteinsdottir, Thorir Einarsson Long, Andri Ólafsson, Elias Eythorsson, Ásbjörn Jónsson, Brynjar Viðarsson, Páll T. Önundarson, Bjarni A. Agnarsson, Róbert Pálmason, Margrét Sigurðardóttir, Ingunn Þorsteinsdóttir, Ísleifur Ólafsson, Stephen J. Harding, Brian G. M. Durie, Thorvardur Jon Love, Sigurdur Y. Kristinsson

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Abstract

Light-chain (LC) monoclonal gammopathy of undetermined significance (MGUS) is a precursor of multiple myeloma (MM) and related conditions. LC-MGUS is characterized by free light-chain (FLC) levels outside defined reference intervals, indirectly indicating underlying plasma cell (PC) monoclonality. Next-generation flow cytometry (NGF) was used to evaluate clonal PC presence in bone marrow (BM) samples from individuals with LC-MGUS in the iStopMM study, aiming to assess the predictive value of the FLC ratio for clonal PC presence and its prognostic implications. BM samples from 61 individuals with LC monoclonal gammopathy were analyzed. Clonal plasma cells were detected in 53.6% of LC-MGUS samples (n = 28) and in all samples from individuals with more advanced conditions (n = 33). The FLC ratio was predictive of clonal PC presence for kappa-involved FLC ratios (p < 0.05; n = 42), with an optimal cutoff of 3.15 (96.7% sensitivity, 91.7% specificity). Of 195 individuals with kappa-involved LC-MGUS in follow-up within the iStopMM study, none with FLC ratios >1.65 to 3.15 progressed to MM (n = 124), whereas 4/71 (5.6%) with FLC ratios >3.15 progressed over median follow-up of 55 months. These findings support using a kappa-involved FLC ratio cutoff of >3.15 to more accurately identify individuals at increased risk of developing symptomatic PC disorders.

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游离轻链比在意义不明的轻链单克隆γ病中的意义：iStopMM筛选研究的流式细胞术亚研究

轻链（LC）单克隆未确定意义γ病（MGUS）是多发性骨髓瘤（MM）及相关疾病的前兆。LC-MGUS的特点是游离轻链（FLC）水平超出定义的参考区间，间接表明潜在的浆细胞（PC）单克隆性。在iStopMM研究中，下一代流式细胞术（NGF）用于评估LC-MGUS患者骨髓（BM）样本中克隆PC的存在，旨在评估FLC比率对克隆PC存在的预测价值及其预后意义。本文对61例LC单克隆伽玛病患者的骨髓样本进行了分析。53.6%的LC-MGUS样本（n = 28）和所有晚期患者的样本（n = 33）中检测到克隆浆细胞。与kappa相关的FLC比值可预测克隆PC的存在(p < 0.05；N = 42)，最佳截止值为3.15（敏感性96.7%，特异性91.7%）。在iStopMM研究中随访的195例kappa相关LC-MGUS患者中，FLC比率为>； 65至3.15的患者无一例进展为MM (n = 124)，而FLC比率为>；3.15的患者有4/71（5.6%）在中位随访55个月期间进展。这些发现支持使用与kappa相关的FLC比率截止值为3.15，以更准确地识别出现症状性PC疾病风险增加的个体。

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来源期刊

Blood Cancer Journal ONCOLOGY-

CiteScore

16.70

自引率

2.30%

发文量

153

审稿时长

>12 weeks

期刊介绍： Blood Cancer Journal is dedicated to publishing high-quality articles related to hematologic malignancies and related disorders. The journal welcomes submissions of original research, reviews, guidelines, and letters that are deemed to have a significant impact in the field. While the journal covers a wide range of topics, it particularly focuses on areas such as: Preclinical studies of new compounds, especially those that provide mechanistic insights Clinical trials and observations Reviews related to new drugs and current management of hematologic malignancies Novel observations related to new mutations, molecular pathways, and tumor genomics Blood Cancer Journal offers a forum for expedited publication of novel observations regarding new mutations or altered pathways.