Induction with Velcade®/Dexamethasone Partially Overcomes the Poor Prognosis of t(4;14), but Not That of Del(17p), in Young Patients with Multiple Myeloma.

Abstract 957

Translocation t(4;14)(p16;q32) has been associated with a poor outcome in multiple myeloma. This poor prognosis has been identified both in patients treated with melphalan-prednisone (MP) and in those treated with high-dose melphalan after a VAD induction. For instance, in 100 patients with t(4;14) treated with VAD and MEL200, the median PFS and OS were 21 months and 41 months, respectively, as compared to 37 months and 65 months for patients lacking the t(4;14) (Moreau et al., Leukemia 2007). Some preliminary studies have suggested that bortezomib (Velcade®) was able to overcome the poor prognosis of the translocation in elderly patients treated with MP-Velcade® (San Miguel et al., NEJM 2008). In order to address this important question, we analyzed 436 patients treated in the IFM, according to the IFM-2005-01 trial, arm B: induction with 4 cycles of Velcade®/Dexamethasone (VD), followed by one or two courses of high-dose melphalan (MEL200). A translocation t(4;14) was observed in 67 of these 436 patients treated with VD (15%), whereas del(17p) was found in 51 patients (11%). Of note, 10 patients presented both the t(4;14) and the del(17p). The median PFS was 25 and 36 months, in patients with or without the t(4;14), respectively (p=0.006). At 3 years, 76% of the patients with t(4;14) were still alive, as compared to 88% of the patients lacking the translocation (p=.003). For comparison, the OS results were respectively 62% (patients with t(4;14)) and 73% (patients lacking the translocation) in patients treated with a VAD induction. Thus, it seems that VD is able to partially overcome the poor prognosis of t(4;14). We also looked at the prognostic value of del(17p) in this series of patients treated with VD. In contrast to the t(4;14) situation, VD was enable to rescue patients with del(17p) (same PFS and OS for patients treated with VD than for those treated with a VAD induction). Thus, this study (by far the largest so far reported) shows that VD as induction before intensification is able to improve the prognosis of patients with t(4;14), but not of those with del(17p).