The Clinical Value of Molecular Subtyping Multiple Myeloma Using Gene Expression Profiling

Using a dataset of 1217 patients with multiple myeloma enrolled in Total Therapies we have examined the impact of novel therapies on molecular and risk subgroups and the clinical value of molecular classification. Bortezomib significantly improved the progression free (PFS) and overall survival (OS) of the MS subgroup. Thalidomide and bortezomib positively impacted the PFS of low risk (LoR) cases defined by the GEP70 signature, whereas high risk (HiR) cases showed no significant changes in outcome. We show that molecular classification is important if response rates are to be used to predict outcomes. The t(11;14) containing CD-1 and CD-2 subgroups showed clear differences in time to response and cumulative response rates but similar PFS and OS. Furthermore, complete remission was not significantly associated with the outcome of the MF subgroup or HiR cases. HiR cases were enriched in the MF, MS and PR subgroups but the poor outcome of these groups was not linked to subgroup specific characteristics like MAF overexpression per se. It is especially important to define risk status if HiR cases are to be managed appropriately because of their aggressive clinical course, high rates of early relapse and the need to maintain therapeutic pressure on the clone.