Early tumor-cell gene expression changes may predict the response to first-line bortezomib-based therapy in patients with newly diagnosed multiple myeloma

Maximizing the response rate to first-line therapy in patients with multiple myeloma (MM) is important because it leads to improved outcome. Gene-expression studies have identified prognostic gene sets in patients receiving bortezomib-based therapy. Comparison of the lists of genes derived from two gene-expression-based models (GEP70, GEP80) showed that they overlap in three genes, namely PSMD4, BIRC5, and KIAA1754. An unanswered question is whether early gene-expression changes can be used as predictors of the response to first-line bortezomib. In this study we aimed to examine the predictive value of gene expression changes for the depth of response after bortezomib-based therapy in newly diagnosed MM. We prospectively assessed the relation between early PSMD4, BIRC5, and KIAA1754 gene expression changes (before therapy and one week later) and the response rate after bortezomib-based therapy in 25 patients with newly diagnosed MM. Gene expression was studied by RT-PCR on CD138-selected plasma cells, and changes were recorded as upregulation, downregulation, or unchanged. Whereas baseline prognostic factors including genetic lesions and stage were not predictive of the response rate, we found that early BIRC5 and KIAA1754 gene-expression changes were significantly associated with the depth of response to bortezomib (p=0.001 and p