Bortezomib/Melphalan/Prednisone (VMP) Followed by Lenalidomide/Dexamethasone (Rd) Overcomes the Poor Prognosis of High-Risk Cytogenetics in Elderly Patients with NDMM

Conference Correspondent  - Conference Correspondent, ASH

Presence of cytogenetic abnormalities (CAs) is considered to be an important prognostic factor in multiple myeloma (MM), with some evidence to suggest that bortezomib-based combinations may overcome the poor prognosis associated with CAs such as t(4;14), t(14;16), or del(17p). However, the prognostic value of 1q gains is unclear. Mateos and colleagues reported results of a preplanned analysis that evaluated the influence of CAs on efficacy outcomes in a cohort of elderly patients with newly diagnosed MM (NDMM) enrolled in the Spanish GEM2010 trial who received bortezomib/melphalan/prednisone (VMP) and lenalidomide/dexamethasone (Rd), in a sequential or alternating treatment regimen.1

A total of 240 patients were randomized to receive 9 cycles of VMP followed by 9 cycles of Rd on either a sequential or alternating regimen (1 cycle of VMP alternating with 1 Rd, up to 18 cycles). FISH analysis of purified plasma cells was performed at diagnosis for t(4;14), t(14;16), del(17p), and 1q gains. Of the 174 patients with FISH data available, a high-risk group (n = 32) consisting of patients harboring t(4;14) and/or t(14;16) and/or del(17p) and a standard-risk group (n = 142) comprising patients without high-risk CA were identified. Overall response rates (ORRs) were similar in the high-risk and standard-risk groups, as well as in the sequential (73% vs 80% ORR) and alternating treatment groups (69% vs 86% ORR). After a median follow-up of 37 months, the alternating treatment regimen in the high-risk group resulted in significantly shorter progression-free survival (PFS) compared with the standard-risk group (24 months vs 36 months, hazard ratio [HR], 2.2; P = .01), which translated to a significantly shorter 4-year overall survival (OS; 27% vs 72%; HR, 3.3; P = .006). However, there were no significant differences in PFS or OS in high-risk and standard-risk patients who received the sequential treatment regimen. Of the 151 patients with 1q information, 76 patients (50.3%) showed 1q gains, defined as the presence of more than 3 copies in at least 10% of plasma cells. The ORR was similar (95% vs 97% in sequential vs alternating regimens) as was the CR rate (55% vs 56%), and there were no differences in ORR, PFS, or OS in patients with or without 1q gains and between the sequential and alternating treatment groups. Based on these results, the authors concluded that sequential administration of the VMP and Rd regimen overcomes the poor prognosis associated with the presence of high-risk CA in elderly patients with NDMM; however, 1q gains had no impact on PFS or OS in this setting.

Mateos M, et al. ASH 2015. Abstract 4243.

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