ADVERTISEMENT
A 12-Gene Signature Accurately Predicts Progression From Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma
Multiple myeloma (MM) is always preceded by a precancerous, asymptomatic phase: monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma. Data from long-term retrospective follow-up studies have shown a 1.0% annual risk of progression from MGUS to MM.
Fumou Sun, PhD, and colleagues presented “A 12 Gene Signature Accurately Predicts Multiple Myeloma Progression from Monoclonal Gammopathy of Undetermined Significance,” at the 64th American Society of Hematology Annual Meeting and Exposition, showing that in a limited population of patients with MGUS, a gene score based on 12 differentiating genes demonstrated noticeable accuracy in predicting 10-year progression from MGUS to MM.
A total of 268 patients with MGUS with gene expression profiles participated in the study, of whom 26 progressed to MM within 10 years (the high-risk group); 242 (the stable group) did not progress to MM. Plasma cells were enriched from bone marrow aspirates to >85% purity and gene expression profiles were performed using 54,613 gene probes. Gene scores were determined by subtracting the averages of the expression of down-regulated genes from those of up-regulated genes.
The researchers analyzed the accuracy of a gene score to predict progression from MGUS to MM by receiver operating characteristic curve (ROC) and its area under the curve (AUC), while they assessed MGUS progression with Kaplan-Meier curves to compare the different groups.
Of the 54,613 probes, 81 were significantly associated with MGUS progression. Following three-fold cross-validation analysis, researchers included the top 12 probes—those that appeared in each validation and maximized concordance between risk and progression—in the final gene signature 12 (GS12). The ROC analysis demonstrated that the GS12 was capable of accurately predicting MGUS progression in the full set of 268 patients, with an overall sensitivity of 65.4% and specificity of 97.5%. Comparisons between GS12 and GEP70, the group’s previously established signature that can identify patients with high-risk MM, showed that GS12 was better than GEP70 at predicting risk of progression from MGUS to MM (73.9% for GS12 vs 18% for GEP70).
“An optimal cut-point for risk of progression by the GS12 score was found to be 2.73, which identified a subset of 23 (8.6%) patients with a 10-year progression probability of 73.9%. The remainder of the 245 patients (91.4%) had a probability of progression of only 3.7%,” Dr Sun presented.
The researchers are optimistic that these results can be applied to larger populations.
“Integration of gene signatures into the routine management of MGUS patients may improve the application of risk-adapted approaches to prevent progression to overt multiple myeloma,” Dr Sun concluded. The researchers are in the process of collecting more samples and incorporating RNA-seq data to determine whether this model can be adapted to predict MGUS progression on a larger scale with current state-of-the-art technologies.
Sun F, Ying J, Cheng Y, et al. A 12 Gene Signature Accurately Predicts Multiple Myeloma Progression from Monoclonal Gammopathy of Undetermined Significance. Presented at the 64th ASH Annual Meeting and Exposition. December 10-13, 2022. Abstract 106.
