Impact of gene expression profiling-based risk stratification in patients with myeloma receiving initial therapy with lenalidomide and dexamethasone

Abstract

Detection of specific chromosomal abnormalities by FISH and metaphase cytogenetics allows risk stratification in multiple myeloma; however, gene expression profiling (GEP) based signatures may enable more specific risk categorization. We examined the utility of 2 GEP-based risk stratification systems among patients undergoing initial therapy with lenalidomide in the context of a phase 3 trial. Among 45 patients studied at baseline, 7 (16%) and 10 (22%), respectively, were high-risk using the GEP70 and GEP15 signatures. The median overall survival for the GEP70 high-risk group was 19 months versus not reached for the rest (hazard ratio = 14.1). Although the medians were not reached, the GEP15 also predicted a poor outcome among the high-risk patients. The C-statistic for the GEP70, GEP15, and FISH based risk stratification systems was 0.74, 0.7, and 0.7, respectively. Here we demonstrate the prognostic value for GEP risk stratification in a group of patients primarily treated with novel agents. This trial was registered at www.clinicaltrials.gov as #NCT00098475.

Figure 1

Impact of risk stratification on overall survival. (A) Kaplan-Meier curves comparing the OS from diagnosis among the high- and standard-risk GEP (GEP70) patients receiving initial therapy with lenalidomide and dexamethasone. (B) Kaplan-Meier curves comparing the OS from diagnosis among the high- and standard-risk patients based on GEP (GEP70) and FISH abnormalities, receiving initial therapy with lenalidomide and dexamethasone. (C) Kaplan-Meier curves comparing the OS from diagnosis among the high- and standard-risk patients based on GEP15 score, receiving initial therapy with lenalidomide and dexamethasone.