title: Clinical value of molecular subtyping multiple myeloma using gene expression profiling.
abstract: Using a data set 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 survival (PFS) and overall survival (OS) of the MMSET (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 MAF/MAFB (MF) subgroup or HiR cases. HiR cases were enriched in the MF, MS and proliferation subgroups, but the poor outcome of these groups was not linked to subgroup-specific characteristics such as 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.
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: N
authors.initials: N
authors.lastname: Weinhold
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Heuck
authors.affiliation: Cancer Research and Biostatistics, Seattle, WA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Rosenthal
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: S
authors.initials: S
authors.lastname: Thanendrarajan
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: C K
authors.initials: CK
authors.lastname: Stein
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: F
authors.initials: F
authors.lastname: Van Rhee
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: M
authors.initials: M
authors.lastname: Zangari
authors.affiliation: Cancer Research and Biostatistics, Seattle, WA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Hoering
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: E
authors.initials: E
authors.lastname: Tian
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: F E
authors.initials: FE
authors.lastname: Davies
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: B
authors.initials: B
authors.lastname: Barlogie
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Morgan
mesh_terms: D018572:Disease-Free Survival; D020869:Gene Expression Profiling; D006801:Humans; D009101:Multiple Myeloma / Q000145:classification / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D012008:Recurrence