title: Clinical, genomic, and imaging predictors of myeloma progression from asymptomatic monoclonal gammopathies (SWOG S0120).
abstract: All cases of clinical myeloma (CMM) are preceded by an asymptomatic monoclonal gammopathy (AMG), classified as either monoclonal gammopathy of undetermined significance (MGUS) or asymptomatic multiple myeloma (AMM). We analyzed data from AMG patients (n = 331) enrolled in a prospective, observational clinical trial (S0120). Baseline data from clinical variables, gene expression profiles (GEP) of purified tumor cells, and findings of magnetic resonance imaging (MRI) were correlated with the risk of progression to CMM requiring therapy. GEP of purified tumor cells revealed that all molecular subtypes of CMM are also represented in the AMG phase. An increased risk score (>-0.26) (based on a 70-gene signature, GEP70) was an independent predictor of the risk of progression to CMM. Combination of elevated serum free light chain, M-spike, and GEP70 risk score identified a subset with high risk (67% at 2 years) of progression to CMM requiring therapy. Importantly, absence of these factors in AMM patients predicted low risk similar to MGUS. Detection of multiple (>1) focal lesions by MRI also conferred an increased risk of progression. These data demonstrate that signatures associated with high-risk CMM impact disease risk and support inclusion of genomic analysis in the clinical management of AMGs.
authors.affiliation: Yale Cancer Center, Yale University, New Haven, CT;
authors.forename: Madhav V
authors.initials: MV
authors.lastname: Dhodapkar
authors.forename: Rachael
authors.initials: R
authors.lastname: Sexton
authors.forename: Sarah
authors.initials: S
authors.lastname: Waheed
authors.forename: Saad
authors.initials: S
authors.lastname: Usmani
authors.forename: Xenofon
authors.initials: X
authors.lastname: Papanikolaou
authors.forename: Bijay
authors.initials: B
authors.lastname: Nair
authors.forename: Nathan
authors.initials: N
authors.lastname: Petty
authors.forename: John D
authors.initials: JD
authors.lastname: Shaughnessy
authors.forename: Antje
authors.initials: A
authors.lastname: Hoering
authors.forename: John
authors.initials: J
authors.lastname: Crowley
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.forename: Bart
authors.initials: B
authors.lastname: Barlogie
mesh_terms: D000368:Aged; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D011230:Precancerous Conditions / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012306:Risk; D053668:Syndecan-1 / Q000378:metabolism; D013997:Time Factors
chemical_list: D007147:Immunoglobulin Light Chains; D053668:Syndecan-1