Benefit of thalidomide (THAL) in total therapy 2 (TT2) of multiple myeloma (MM) exhibiting both cytogenetic abnormalities (CA) and low-risk (LR) by gene expression profiling (GEP)

Abstract

8590 Background: We recently reported an update of TT2 and observed an unexpected preferential benefit from THAL for OS in the subgroup of patients with CA (Blood, 2008). We now re-examined these results with further follow-up of 81 months in the context of GEP-defined risk. Methods: OS and EFS were examined in the 668 patients enrolled in TT2 according to treatment arm, CA status and by GEP risk status. Results: Median overall and event-free survival (OS, EFS) are 9yr and 5yr, with a significant benefit from THAL v the control arm (p=0.04, p=0.0004). We confirmed the ongoing unique survival benefit of THAL in the CA group with 6-yr OS estimates of 53% v 35% (p<0.001), while patients not exhibiting CA had similar OS of 70% and 68%. EFS was superior with THAL regardless of CA status, 56% v 45% without CA (p=0.02) and 38% v 20% with CA (p=0.008). With respect to GEP, THAL benefited the LR group with 6-yr OS/EFS rates of 73%/56% v 63%/36% without THAL (p=0.10/p=0.002); the corresponding data for high-risk (HR) patients showed OS/EFS with THAL of 35%/19% v 15%/10% without THAL (p=0.36/p=0.43). When examined in the context of both GEP and CA, THAL only benefited the 33 patients with both CA and LR with 6-yr OS of 72% v 37% among the 47 without THAL (p=0.003). For the remaining subgroups (CA/HR; no CA/LR, no CA/HR), the addition of THAL did not impact OS. Conclusions: The unique benefit of THAL to the CA/LR subgroup may be linked to its greater efficacy in proliferative MM (enabling CA detection) that can only be sustained in the LR (lacking amplification of 1q21?) but not in the HR subset. The concomitant examinations of MM genetics by both GEP and cytogenetics enabled the discovery of this subgroup-specific treatment benefit. Data on TT3 with the addition of bortezomib will be presented in the context of the CA/GEP-risk scenario. [Table: see text]