Gene Expression Changes in Myeloma Cells Following Short Term In-vivo Drug Exposure

In vivo changes of gene expression profiles (GEP) of tumor cells 48hr after single agent therapy may vary by treatment and provide added predictive power over baseline GEP information. In newly diagnosed patients with multiple myeloma (MM), GEP data were obtained on tumor cells prior to and 48hr after dexamethasone (n=45) or thalidomide treatment (n=42); in case of relapsed MM, GEP data were obtained prior to (n=36) and after (n=19) lenalidomide administration. Dexamethasone and thalidomide induced both common and unique GEP changes. Combined baseline and 48hr changes of GEP in a subset of genes that were discovered in newly diagnosed MM also predicted event-free and overall survival in relapsed patients receiving lenalidomide. Combined with baseline molecular features, changes in GEP following short-term single agent treatment may help guide treatment decisions for patients with MM. The genes whose altered expression is related to eventual survival may also point to mechanisms of action and resistance to different classes of drugs.

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