TY - JOUR
T1 - Clinical, genomic, and imaging predictors of myeloma progression from asymptomatic monoclonal gammopathies (swog s0120)
AU - Dhodapkar, Madhav V.
AU - Sexton, Rachael
AU - Waheed, Sarah
AU - Usmani, Saad
AU - Papanikolaou, Xenofon
AU - Nair, Bijay
AU - Petty, Nathan
AU - Shaughnessy, John D.
AU - Hoering, Antje
AU - Crowley, John
AU - Orlowski, Robert Z.
AU - Barlogie, Bart
PY - 2014/1/2
Y1 - 2014/1/2
N2 - 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 5 331) 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. This trial was registered at www.clinicaltrials.gov as # NCT00900263. (Blood. 2014;123(1):78-85).
AB - 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 5 331) 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. This trial was registered at www.clinicaltrials.gov as # NCT00900263. (Blood. 2014;123(1):78-85).
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U2 - 10.1182/blood-2013-07-515239
DO - 10.1182/blood-2013-07-515239
M3 - Article
C2 - 24144643
AN - SCOPUS:84891819060
SN - 0006-4971
VL - 123
SP - 78
EP - 85
JO - Blood
JF - Blood
IS - 1
ER -