title: Testing standard and genetic parameters in 220 patients with multiple myeloma with complete data sets: superiority of molecular genetics.
abstract: Prognostic models for multiple myeloma have been fraught with tremendous heterogeneity in outcome among subgroups. In the context of Total Therapy 2, a tandem transplant trial for newly diagnosed myeloma, comprehensive information was available in 220 patients on standard prognostic factors (SPF), magnetic resonance imaging (MRI)-defined focal lesions, cytogenetic abnormalities (CA), fluorescence-in-situ-hybridisation (FISH)-derived amplification of chromosome 1q21 (amp1q21) and deletion of 13q14, as well as gene expression profiling (GEP). Five multivariate analysis-based survival models were derived, utilising SPF only (model 1), with progressive addition of CA (model 2), MRI (model 3), FISH (model 4) and GEP (model 5). The R(2) value, a measure of accounting for clinical outcome variability, increased progressively from 18% in model 1 to 38% in model 5. The hazard ratio for overall survival was highest for GEP (3.07, P < 0.001) followed by amp1q21 (1.71, P = 0.05). According to the presence of none (49%), one (35%) or both of these two risk features (16%), 3-year survival decreased progressively from 92% to 78% to 43% (P < 0.0001). Thus, the dominance over other prognostic parameters of molecular genetics justifies the generation of quantitative reverse transcription polymerase chain reaction methodology ('MM genetic kit') for the optimal risk stratification of patients participating in therapeutic trials.
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. hebertkahlan@uams.edu
authors.forename: John D
authors.initials: JD
authors.lastname: Shaughnessy
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Haessler
authors.forename: Frits
authors.initials: F
authors.lastname: van Rhee
authors.forename: Elias
authors.initials: E
authors.lastname: Anaissie
authors.forename: Mauricio
authors.initials: M
authors.lastname: Pineda-Roman
authors.forename: Michele
authors.initials: M
authors.lastname: Cottler-Fox
authors.forename: Klaus
authors.initials: K
authors.lastname: Hollmig
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zangari
authors.forename: Abid
authors.initials: A
authors.lastname: Mohiuddin
authors.forename: Yazan
authors.initials: Y
authors.lastname: Alsayed
authors.forename: Monica
authors.initials: M
authors.lastname: Grazziutti
authors.forename: Joshua
authors.initials: J
authors.lastname: Epstein
authors.forename: John
authors.initials: J
authors.lastname: Crowley
authors.forename: Bart
authors.initials: B
authors.lastname: Barlogie
mesh_terms: D000328:Adult; D000368:Aged; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1; D020732:Cytogenetic Analysis; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D015999:Multivariate Analysis; D011379:Prognosis; D012307:Risk Factors