Chromosome 1q21 gains confer inferior outcomes in multiple myeloma treated with bortezomib but copy number variation and percentage of plasma cells involved have no additional prognostic value
Chromosome 1q21 gains confer inferior outcomes in multiple myeloma treated with bortezomib but copy number variation and percentage of plasma cells involved have no additional prognostic value
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染色体 1q21 增加导致用硼替佐米治疗的多发性骨髓瘤预后较差，但拷贝数变异和所涉及浆细胞的百分比没有额外的预后价值
DOI：
10.3324/haematol.2013.088211
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发表时间：
2014-02-01
期刊：
影响因子：
10.1
通讯作者：
Qiu, Lugui
中科院分区：
文献类型：
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作者：
An, Gang;Xu, Yan;Qiu, Lugui
染色体1 q21畸变尚未成为常规临床试验的一部分，其在多发性骨髓瘤中的作用仍在研究中。拷贝数变异和浆细胞百分比的预后价值尚不清楚。在本研究中，我们分析了一系列290例新诊断的多发性骨髓瘤患者的预后价值，这些患者在一项前瞻性、非随机临床试验（BDH 2008/02）中接受治疗。我们发现复发时1 q21畸变的发生率增加，但其拷贝数和涉及的细胞比例没有变化。1 q21的增加对接受沙利度胺治疗的患者的生存率没有影响，但对接受硼替佐米化疗的患者预后明显较差，是无进展生存期的独立不良预后因素（HR 3.831; 95%CI：2.125-6.907; P<0.001）和总生存期（HR 3.245; 95%CI：1.555-6.773; P=0.002）。引人注目的是，我们的研究结果表明，拷贝数变异和克隆大小窝藏1 q21增益进行没有额外的预后价值和1 q21增益的患者没有显着受益于方案纳入硼替佐米。我们的研究结果表明，三个拷贝的1 q21和20%的浆细胞与这种异常足以赋予硼替佐米耐药。因此，在接受硼替佐米治疗的多发性骨髓瘤中，染色体1 q21增益应被视为高风险特征。
Chromosome 1q21 aberrations have not been yet been made part of routine clinical tests and their effect in multiple myeloma is still under investigation. The prognostic value of copy number variation and percentage of plasma cells involved have remained unclear. In the present study, we analyzed the prognostic value of 1q21 in a series of 290 cases of newly diagnosed multiple myeloma treated in a prospective, non-randomized clinical trial (BDH 2008/02). We found that incidence of 1q21 aberration increased at relapse, but its copy numbers and proportion of cells involved did not change. Gains of 1q21 had no impact on survival in patients receiving thalidomide-based treatment but conferred a significantly inferior prognosis in patients under bortezomib-based chemotherapy and was an independent adverse prognostic factor for progression free survival (HR 3.831; 95%CI: 2.125–6.907; P<0.001) and overall survival (HR 3.245; 95%CI: 1.555–6.773; P=0.002). Strikingly, our results showed that the copy number variation and clone size harboring 1q21 gains carried no additional prognostic value and patients with 1q21 gains did not benefit significantly from regimens incorporating bortezomib. Our results indicate that three copies of 1q21 and 20% of plasma cells with this abnormality were enough to confer bortezomib resistance. Therefore, chromosome 1q21 gains should be considered a high-risk feature in multiple myeloma receiving bortezomib therapy.