Extramedullary disease portends poor prognosis in multiple myeloma and is over-represented in high-risk disease even in the era of novel agents
Extramedullary disease portends poor prognosis in multiple myeloma and is over-represented in high-risk disease even in the era of novel agents
复制标题
DOI：
10.3324/haematol.2012.065698
复制
发表时间：
2012-11-01
期刊：
影响因子：
--
通讯作者：
Barlogie, Bart
中科院分区：
文献类型：
--
作者：
Usmani, Saad Z.;Heuck, Christoph;Barlogie, Bart
背景髓外疾病是多发性骨髓瘤的一种罕见表现，可能伴随新诊断的疾病，也可能随着疾病进展或复发而发展。我们评估了这种疾病特征在新型药物背景下对患者预后的影响。 设计和方法我们分析了参加全面治疗方案的 936 名多发性骨髓瘤患者、接受非全面治疗方案的 240 名患者和 789 名非方案患者的髓外疾病的临床和生物学特征，所有这些患者都进行了基线正电子发射断层扫描，以记录诊断时的髓外疾病及其后续发展 结果诊断时髓外疾病最常见的部位是皮肤和软组织，而肝脏受累是疾病复发或进展时髓外疾病的显着特征。无论采用何种治疗方法，髓外疾病均与较短的无进展生存期和总生存期以及贫血、血小板减少症、血清乳酸脱氢酶升高、细胞遗传学异常以及单变量分析中 70 和 80 基因风险模型中的高风险特征的存在相关。逻辑回归的多变量分析表明，这种疾病特征在中心体指数升高（通过基因表达谱确定）的患者以及更容易复发的骨髓瘤分子亚型中更为普遍。其中包括 MF 亚型（也称为“MAF”亚型，与染色体易位 14、16 或 14；20 所见的 MAF 基因过度表达相关）和 PR 亚型（也称为“增殖”亚型，与促增殖基因过度表达相关）。结论这些数据表明，髓外疾病在基因组定义的高危多发性骨髓瘤中更为普遍。 即使在新药时代，骨髓瘤也与较短的无进展生存期和总生存期相关。分析中包含的所有临床试验均已在 www.clinicaltrials.gov 注册（NCT00083551、NCT00083876、NCT00081939、NCT00572169、NCT00644228、NCT00002548、NCT00734877）。
BackgroundExtramedullary disease is an uncommon manifestation in multiple myeloma and can either accompany newly diagnosed disease or develop with disease progression or relapse. We evaluated the impact of this disease feature on patients' outcome in the context of novel agents.Design and MethodsWe analyzed clinical and biological features of extramedullary disease in 936 patients with multiple myeloma enrolled in Total Therapy protocols, 240 patients in non-Total Therapy protocols, and 789 non-protocol patients, all of whom had baseline positron emission tomography scans to document extramedullary disease at diagnosis and its subsequent development at the time of disease progression or relapse.ResultsThe most common sites for extramedullary disease at diagnosis were skin and soft tissue whereas liver involvement was the striking feature in extramedullary disease at disease relapse or progression. Regardless of therapy, extramedullary disease was associated with shorter progression-free and overall survival, as well as the presence of anemia, thrombocytopenia, elevated serum lactate dehydrogenase, cytogenetic abnormalities, and high-risk features in 70- and 80-gene risk models in univariate analysis. Multivariate analysis with logistic regression revealed that this disease feature was more prevalent in patients with an elevated centrosome index, as determined by gene expression profiling, as well as in myeloma molecular subtypes that are more prone to relapse. These include the MF subtype (also called the "MAF" subtype, associated with over-expression of the MAF gene seen with chromosome translocation 14; 16 or 14; 20) and the PR subtype (also called the "Proliferation" subtype, associated with overexpression of pro-proliferative genes).ConclusionsThese data show that extramedullary disease is more prevalent in genomically defined high-risk multiple myeloma and is associated with shorter progression-free survival and overall survival, even in the era of novel agents. All clinical trials included in the analyses were registered with www.clinicaltrials.gov (NCT00083551, NCT00083876, NCT00081939, NCT00572169, NCT00644228, NCT00002548, NCT00734877).