With advent of several treatment options in multiple myeloma, a selection of effective regimen has become an important issue. Use of GEP is considered an important tool in predicting outcome; however, it is unclear whether such genomic analysis alone can adequately predict therapeutic response. We evaluated ability of GEP to predict complete response in MM. GEP from pre-treatment MM cells from 136 uniformly treated MM patients with response data on an IFM, France led study were analyzed. To evaluate variability in predictive power due to microarray platform or treatment types, additional datasets from three different studies (n=511) were analyzed using same methods. We used several machine learning methods to derive a prediction model using training and test subsets of the original four datasets. Among all methods employed for GEP-based CR predictive capability, we got accuracy range of 56% to 78% in test datasets and no significant difference with regard to GEP platforms, treatment regimens or in newly-diagnosed or relapsed patients. Importantly, permuted P-value showed no statistically significant CR predictive information in GEP data. This analysis suggests that GEP-based signature has limited power to predict CR in MM, highlighting the need to develop comprehensive predictive model using integrated genomics approach.Leukemia accepted article peview online, 15 April 2014. doi:10.1038/leu.2014.140.