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Myeloma

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

Leukemia volume 27, pages 1738–1744 (2013)Cite this article

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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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Acknowledgements

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.

Author contributions

SVR and SKK designed the research, analyzed the data, wrote and edited the manuscript. VG, RF, AD, WIG, DL, RPK, JAL and RAK participated in data interpretation, reviewed the manuscript and provided critical comments. All authors reviewed and approved the final manuscript.

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Authors and Affiliations

  1. Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA

    S V Rajkumar, V Gupta, A Dispenzieri, W I Gonsalves, J A Lust, R A Kyle & S K Kumar

  2. Department of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ, USA

    R Fonseca

  3. Department of Biostatistics, Mayo Clinic, Rochester, MN, USA

    D Larson

  4. Department of Laboratory Medicine, Mayo Clinic, Rochester, MN, USA

    R P Ketterling

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Competing interests

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.

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Rajkumar, S., Gupta, V., Fonseca, R. et al. Impact of primary molecular cytogenetic abnormalities and risk of progression in smoldering multiple myeloma. Leukemia 27, 1738–1744 (2013). https://doi.org/10.1038/leu.2013.86

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