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. 2013 Aug;27(8):1738-44.
doi: 10.1038/leu.2013.86. Epub 2013 Mar 21.

Impact of primary molecular cytogenetic abnormalities and risk of progression in smoldering multiple myeloma

S V Rajkumar  1 , V Gupta, R Fonseca, A Dispenzieri, W I Gonsalves, D Larson, R P Ketterling, J A Lust, R A Kyle, S K Kumar
Affiliations

Impact of primary molecular cytogenetic abnormalities and risk of progression in smoldering multiple myeloma

S V Rajkumar et al. Leukemia. 2013 Aug.

Abstract

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.

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Conflict of interest statement

CONFLICT OF INTEREST

Dr Fonseca has received a patent for the prognostication of MM based on genetic categorization of the disease. He has received consulting fees from Medtronic, Otsuka, Celgene, Genzyme, BMS, Lilly, Onyx, Binding Site, Millenium and AMGEN. He also has sponsored research from Cylene and Onyx. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
TTP of SMM to symptomatic MM. The TTP was significantly inferior in patients with the t(4;14) (HR) compared with patients with t(11;14) (SR), median 28 versus 55 months, respectively, P = 0.025.
Figure 2
Figure 2
TTP of SMM to symptomatic MM according to four risk groups defined by primary cytogenetic abnormalities. The median TTP was 28 months with the t(4;14) (HR), 34 months with trisomies alone (IR), 55 months with t(11;14), MAF translocations, other/unknown 14q32 translocations, monosomy13/del(13q) without other abnormalities, and those with both trisomies and IgH translocations (SR), and not reached in patients with no detectable abnormalities (LR), P = 0.001.
Figure 3
Figure 3
TTP of SMM to symptomatic MM according to modified cytogenetically defined risk-based classification. The median TTP was 24 months with the t(4;14)/del(17p) (HR), 34 months with trisomies alone (IR), 55 months with t(11;14), MAF translocations, other/unknown 14q32 translocations, monosomy13/del(13q) without other abnormalities, and those with both trisomies and IgH translocations except t(4;14) (SR), and not reached in patients with no detectable abnormalities (LR), P = 0.002.
Figure 4
Figure 4
Overall survival from time of diagnosis of SMM. Survival was significantly inferior in patients with the t(4;14) (HR) compared with patients with t(11;14) (SR), median 105 versus 147 months, respectively, P = 0.036.
Figure 5
Figure 5
Overall survival from diagnosis of symptomatic MM according to the four cytogenetically defined risk groups. Survival was 51 months with t(4;14) (HR), 77 months with trisomies alone (IR), 86 months with t(11;14), MAF translocations, other/unknown 14q32 translocations, monosomy13/del(13q) without other abnormalities, and those with both trisomies and IgH translocations (SR), and 112 months in patients with no detectable abnormalities (LR), P = 0.04.
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References

    1. Rajkumar SV. Treatment of multiple myeloma. Nature Rev Clin Oncol. 2011;8:479–491. - PMC - PubMed
    1. Rajkumar SV. Multiple myeloma: 2013 update on diagnosis, risk-stratification, and management. Am J Hematol. 2013;88:225–235. - PubMed
    1. Kumar SK, Lee JH, Lahuerta JJ, Morgan G, Richardson PG, Crowley J, et al. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter international myeloma working group study. Leukemia. 2012;26:149–157. - PMC - PubMed
    1. Sinha S, Lacy M, Mikhael J, Hayman S, Buadi F, Detweiler-Short K, et al. Response to salvage therapies and outcome in patients with multiple myeloma relapsing after pomalidomide therapy. Leukemia. 2012;26:839–841. - PubMed
    1. Mohty B, El-Cheikh J, Yakoub-Agha I, Avet-Loiseau H, Moreau P, Mohty M. Treatment strategies in relapsed and refractory multiple myeloma: a focus on drug sequencing and ‘retreatment’ approaches in the era of novel agents. Leukemia. 2012;26:73–85. - PubMed

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