Clinical, genomic, and imaging predictors of myeloma progression from asymptomatic monoclonal gammopathies (SWOG S0120)
Clinical, genomic, and imaging predictors of myeloma progression from asymptomatic monoclonal gammopathies (SWOG S0120)
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DOI：
10.1182/blood-2013-07-515239
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发表时间：
2014-01-02
期刊：
影响因子：
20.3
通讯作者：
Barlogie, Bart
中科院分区：
文献类型：
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作者：
Dhodapkar, Madhav V.;Sexton, Rachael;Barlogie, Bart
所有临床骨髓瘤（CMM）病例之前均存在无症状单克隆丙种球蛋白病（AMG），分类为意义不明的单克隆丙种球蛋白病（MGUS）或无症状多发性骨髓瘤（AMM）。我们分析了一项前瞻性、观察性临床试验（S 0120）中入组的AMG患者（n = 331）的数据。来自临床变量、纯化肿瘤细胞的基因表达谱（GEP）和磁共振成像（MRI）结果的基线数据与进展为需要治疗的CMM的风险相关。纯化的肿瘤细胞的GEP显示CMM的所有分子亚型也在AMG期中表现。增加的风险评分（>-0.26）（基于70个基因签名，GEP 70）是进展为CMM的风险的独立预测因子。血清游离轻链、M-峰和GEP 70风险评分升高的组合确定了一个亚组，该亚组具有进展为需要治疗的CMM的高风险（2年时为67%）。重要的是，在AMM患者中缺乏这些因素预示着与MGUS相似的低风险。通过MRI检测到多个（>1个）局灶性病变也增加了进展风险。这些数据表明，与高风险CMM相关的特征会影响疾病风险，并支持将基因组分析纳入AMG的临床管理。本试验在www.clinicaltrials.gov上注册为#NCT 00900263。
All cases of clinical myeloma (CMM) are preceded by an asymptomatic monoclonal gammopathy (AMG), classified as either monoclonal gammopathy of undetermined significance (MGUS) or asymptomatic multiple myeloma (AMM). We analyzed data from AMG patients (n = 331) enrolled in a prospective, observational clinical trial (S0120). Baseline data from clinical variables, gene expression profiles (GEP) of purified tumor cells, and findings of magnetic resonance imaging (MRI) were correlated with the risk of progression to CMM requiring therapy. GEP of purified tumor cells revealed that all molecular subtypes of CMM are also represented in the AMG phase. An increased risk score (>-0.26) (based on a 70-gene signature, GEP70) was an independent predictor of the risk of progression to CMM. Combination of elevated serum free light chain, M-spike, and GEP70 risk score identified a subset with high risk (67% at 2 years) of progression to CMM requiring therapy. Importantly, absence of these factors in AMM patients predicted low risk similar to MGUS. Detection of multiple (>1) focal lesions by MRI also conferred an increased risk of progression. These data demonstrate that signatures associated with high-risk CMM impact disease risk and support inclusion of genomic analysis in the clinical management of AMGs. This trial was registered at www.clinicaltrials.gov as # NCT00900263.