Persistence of minimal residual disease (MRD) after treatment for myeloma predicts inferior outcomes, but within MRD-positive patients there is great heterogeneity with both early and very late relapses. Among different MRD techniques, flow cytometry provides additional information about antigen expression on tumor cells, which could potentially contribute to stratify MRD-positive patients. We investigated the prognostic value of those antigens required to monitor MRD in 1265 newly diagnosed patients enrolled in the GEM2000, GEM2005MENOS65, GEM2005MAS65 and GEM2010MAS65 protocols. Overall, CD19^pos, CD27^neg, CD38^lo, CD45^pos, CD81^pos, CD117^neg and CD138^lo expression predicted inferior outcomes. Through principal component analysis, we found that simultaneous CD38^lowCD81^posCD117^neg expression emerged as the most powerful combination with independent prognostic value for progression-free survival (HR:1.69; P=0.002). This unique phenotypic profile retained prognostic value among MRD-positive patients. We then used next-generation flow to determine antigen stability throughout the course of the disease, and found that the expression of antigens required to monitor MRD is mostly stable from diagnosis to MRD stages, except for CD81 whose expression progressively increased from baseline to chemoresistant tumor cells (14 vs 28%). Altogether, we showed that the phenotypic profile of tumor cells provides additional prognostic information, and could be used to further predict risk of relapse among MRD-positive patients.

中文翻译：

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抗原表达在多发性骨髓瘤中的预后价值：一项PETHEMA / GEM研究对12例65例患者进行了连续四个临床试验。

骨髓瘤治疗后持续存在的最小残留疾病（MRD）预测结果较差，但在MRD阳性患者中，早期和晚期复发均存在很大的异质性。在不同的MRD技术中，流式细胞术提供了有关肿瘤细胞上抗原表达的更多信息，这可能有助于对MRD阳性患者进行分层。我们调查了在GEM2000，GEM2005MENOS65，GEM2005MAS65和GEM2010MAS65方案中招募的1265名新诊断患者中监测MRD所需的那些抗原的预后价值。总体而言，CD19 ^pos，CD27 ^neg，CD38 ^lo，CD45 ^pos，CD81 ^pos，CD117 ^neg和CD138 ^lo表达预测的结果较差。通过主成分分析，我们发现同时CD38^低CD81 ^POS CD117^负这种表达成为无进展生存期具有独立预后价值的最有力组合（HR：1.69； P = 0.002）。这种独特的表型特征保留了MRD阳性患者的预后价值。然后，我们使用下一代流程来确定整个疾病过程中的抗原稳定性，并发现从诊断到MRD阶段，监测MRD所需的抗原的表达大部分是稳定的，除了CD81的表达从基线逐渐升高到对化学耐药的肿瘤而言细胞（14％对28％）。总之，我们表明肿瘤细胞的表型特征提供了更多的预后信息，并可用于进一步预测MRD阳性患者中复发的风险。