TY - JOUR
T1 - Impact of primary molecular cytogenetic abnormalities and risk of progression in smoldering multiple myeloma
AU - Rajkumar, S. V.
AU - Gupta, V.
AU - Fonseca, R.
AU - Dispenzieri, A.
AU - Gonsalves, W. I.
AU - Larson, D.
AU - Ketterling, R. P.
AU - Lust, J. A.
AU - Kyle, R. A.
AU - Kumar, S. K.
N1 - Funding Information:
This work was supported by National Cancer Institute grants CA168762, CA 107476, CA 100707, CA90297052 and CA 83724. Also supported in part by ECOG CA 21115T, the Jabbs Foundation (Birmingham, UK), the Henry J. Predolin Foundation, USA, Mayo Clinic Cancer Center and the Mayo Foundation. Rafael Fonseca is a Clinical Investigator of the Damon Runyon Cancer Research Fund.
PY - 2013/8
Y1 - 2013/8
N2 - We studied 351 patients with smoldering multiple myeloma (SMM) in whom the underlying primary molecular cytogenetic subtype could be determined based on cytoplasmic immunoglobulin fluorescent in situ hybridization studies. Hundred and fifty-four patients (43.9%) had trisomies, 127 (36.2%) had immunoglobulin heavy chain (IgH) translocations, 14 (4%) both trisomies and IgH translocations, 53 (15.1%) no abnormalities detected and 3 (0.9%) had monosomy13/del(13q) in the absence of any other abnormality. Among 127 patients with IgH translocations, 57 were t(11;14), 36 t(4;14), 11 musculoaponeurotic fibrosarcoma (MAF) translocations, and 23 other or unknown IgH translocation partner. Time to progression (TTP) to symptomatic multiple myeloma was significantly shorter in patients with the t(4;14) compared with patients with t(11;14), median 28 versus 55 months, respectively, P=0.025. The median TTP was 28 months with t(4;14) (high-risk), 34 months with trisomies alone (intermediate-risk), 55 months with t(11;14), MAF translocations, other/unknown IgH translocations, monosomy13/del(13q) without other abnormalities, and those with both trisomies and IgH translocations (standard-risk), and not reached in patients with no detectable abnormalities (low-risk), P=0.001. There was a trend to shorter TTP with deletion 17p (median TTP, 24 months). Overall survival from diagnosis of SMM was significantly inferior with t(4;14) compared with t(11;14), median 105 versus 147 months, respectively, P=0.036.
AB - We studied 351 patients with smoldering multiple myeloma (SMM) in whom the underlying primary molecular cytogenetic subtype could be determined based on cytoplasmic immunoglobulin fluorescent in situ hybridization studies. Hundred and fifty-four patients (43.9%) had trisomies, 127 (36.2%) had immunoglobulin heavy chain (IgH) translocations, 14 (4%) both trisomies and IgH translocations, 53 (15.1%) no abnormalities detected and 3 (0.9%) had monosomy13/del(13q) in the absence of any other abnormality. Among 127 patients with IgH translocations, 57 were t(11;14), 36 t(4;14), 11 musculoaponeurotic fibrosarcoma (MAF) translocations, and 23 other or unknown IgH translocation partner. Time to progression (TTP) to symptomatic multiple myeloma was significantly shorter in patients with the t(4;14) compared with patients with t(11;14), median 28 versus 55 months, respectively, P=0.025. The median TTP was 28 months with t(4;14) (high-risk), 34 months with trisomies alone (intermediate-risk), 55 months with t(11;14), MAF translocations, other/unknown IgH translocations, monosomy13/del(13q) without other abnormalities, and those with both trisomies and IgH translocations (standard-risk), and not reached in patients with no detectable abnormalities (low-risk), P=0.001. There was a trend to shorter TTP with deletion 17p (median TTP, 24 months). Overall survival from diagnosis of SMM was significantly inferior with t(4;14) compared with t(11;14), median 105 versus 147 months, respectively, P=0.036.
KW - biomarker
KW - cytogenetics
KW - prognosis
KW - smoldering multiple myeloma
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U2 - 10.1038/leu.2013.86
DO - 10.1038/leu.2013.86
M3 - Article
C2 - 23515097
AN - SCOPUS:84881477133
SN - 0887-6924
VL - 27
SP - 1738
EP - 1744
JO - Leukemia
JF - Leukemia
IS - 8
ER -