Gene expression profiling (GEP)-defined risk and molecular subgroups assessed at baseline and at relapse: Collective impact on post-relapse survival of multiple myeloma (MM) treated with total therapies 2 and 3

Abstract

8589 Background: GEP-defined risk has evolved as the most robust predictor of overall and event-free survival (OS, EFS) in MM with TT2 and TT3 protocols, distinguishing 85% with low-risk (LR) and 15% with high-risk (HR). Upon relapse, the original risk designation may change typically in the direction LR to HR. Here we examine, among patients with available GEP data at baseline (BL) and relapse (REL), the contributions of both observations on post-relapse survival (PRS). Methods: Paired REL-BL GEP data were available in 77 patients, while information on metaphase cytogenetic abnormalities (CA) was obtained in 76 patients at both time-points. Results: PRS was significantly affected by both BL and REL HR status so that, among the 52 patients with LR at BL, HR status at REL conferred significantly poorer outcome compared to those with LR at REL (p=0.0005) with 30-mo estimates of 71% v 13%; likewise, among the 25 patients with HR at baseline, HR present also at relapse further diminished PRS (p=0.09) with 30-mo estimates in both settings of less than 20%. Similar considerations for CA status revealed, among the 29 patients without CA at BL, marked attrition of PRS with CA v no CA at REL with 30-mo estimates of 29% v 81% (p=0.04); for the 47 patients with CA at BL, CA also at REL further diminished the poor PRS from 46% to 22% (p=0.06). When all standard BL and REL prognostic factors were examined in a multivariate model, GEP-derived HR contributed to poor PRS both when present at BL (HR=2.79, p=0.005) and at REL (HR=2.77, p=0.002), in addition to CA at BL (HR=2.44, p=0.018). Conclusions: In estimating PRS in TT protocols, genetic characteristics at BL (HR, CA) have enduring adverse consequences aggravated further by HR status at REL. Therefore, in HR/CA BL settings, aiming at REL prevention appears as the best overall treatment strategy. [Table: see text]