Abstract：
The International Myeloma Working Group recently fully incorporated 18F-FDG PET into multiple myeloma (MM) diagnosis and response evaluation. Moreover, a few studies demonstrated the prognostic value of several biomarkers extracted from this imaging at baseline. Before these 18F-FDG PET biomarkers could be fully endorsed as risk classifiers by the hematologist community, further characterization of underlying molecular aspects was necessary. Methods: Reported prognostic biomarkers (18F-FDG avidity, SUVmax, number of focal lesions, presence of paramedullary disease [PMD] or extramedullary disease) were extracted from 18F-FDG PET imaging at baseline in a group of 139 patients from CASSIOPET, a companion study of the CASSIOPEIA cohort (ClinicalTrials.gov identifier NCT02541383). Transcriptomic analyses using RNA sequencing were realized on sorted bone marrow plasma cells from the same patients. An association with a high-risk gene expression signature (IFM15), molecular classification, progression-free survival, a stringent clinical response, and minimal residual disease negativity were explored. Results:18F-FDG PET results were positive in 79.4% of patients; 14% and 11% of them had PMD and extramedullary disease, respectively. Negative 18F-FDG PET results were associated with lower levels of expression of hexokinase 2 (HK2) (fold change, 2.1; adjusted P = 0.04) and showed enrichment for a subgroup of patients with a low level of bone disease. Positive 18F-FDG PET results displayed 2 distinct signatures: either high levels of expression of proliferation genes or high levels of expression of GLUT5 and lymphocyte antigens. PMD and IFM15 were independently associated with a lower level of progression-free survival, and the presence of both biomarkers defined a group of \"double-positive\" patients at very high risk of progression. PMD and IFM15 were related neither to minimal residual disease assessment nor to a stringent clinical response. Conclusion: Our study confirmed and extended the association between imaging biomarkers and transcriptomic programs in MM. The combined prognostic value of PMD and a high-risk IFM15 signature may help define MM patients with a very high risk of progression.
摘要：
国际骨髓瘤工作组最近将18F-FDGPET完全纳入多发性骨髓瘤（MM）的诊断和反应评估。此外，一些研究表明,从基线成像中提取的几种生物标志物具有预后价值.在这些18F-FDGPET生物标志物被血液学家社区完全认可为风险分类器之前，进一步表征潜在的分子方面是必要的。方法：报告的预后生物标志物(18F-FDG亲和力，SUVmax,局灶性病变的数量，在一组139名来自CASSIOPET的患者中，基线时从18F-FDGPET成像中提取髓旁疾病[PMD]或髓外疾病的存在），CASSIOPEIA队列的伴随研究(ClinicalTrials.gov标识符NCT02541383)。在来自同一患者的分选的骨髓浆细胞上实现了使用RNA测序的转录组学分析。与高风险基因表达特征（IFM15）相关，分子分类，无进展生存期,严格的临床反应，并探讨了微小残留病的负性。结果:79.4%的患者18F-FDGPET结果为阳性;14%和11%的患者有PMD和髓外疾病,分别。18F-FDGPET结果阴性与己糖激酶2（HK2）表达水平降低相关（倍数变化，2.1；调整后的P=0.04），并显示出低水平骨病患者亚组的富集。阳性18F-FDGPET结果显示2个不同的特征:增殖基因的高水平表达或GLUT5和淋巴细胞抗原的高水平表达。PMD和IFM15与较低水平的无进展生存期独立相关，两种生物标志物的存在定义了一组进展风险非常高的“双阳性”患者。PMD和IFM15既不与微小残留病评估相关，也不与严格的临床反应相关。结论：我们的研究证实并扩展了MM中成像生物标志物与转录组程序之间的关联。PMD和高风险IFM15特征的组合预后价值可能有助于定义具有非常高的进展风险的MM患者。
