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Multiple Myeloma, Gammopathies

Clinical value of molecular subtyping multiple myeloma using gene expression profiling

Leukemia volume 30, pages 423–430 (2016)Cite this article

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Abstract

Using a data set of 1217 patients with multiple myeloma enrolled in Total Therapies, we have examined the impact of novel therapies on molecular and risk subgroups and the clinical value of molecular classification. Bortezomib significantly improved the progression-free survival (PFS) and overall survival (OS) of the MMSET (MS) subgroup. Thalidomide and bortezomib positively impacted the PFS of low-risk (LoR) cases defined by the GEP70 signature, whereas high-risk (HiR) cases showed no significant changes in outcome. We show that molecular classification is important if response rates are to be used to predict outcomes. The t(11;14)-containing CD-1 and CD-2 subgroups showed clear differences in time to response and cumulative response rates but similar PFS and OS. Furthermore, complete remission was not significantly associated with the outcome of the MAF/MAFB (MF) subgroup or HiR cases. HiR cases were enriched in the MF, MS and proliferation subgroups, but the poor outcome of these groups was not linked to subgroup-specific characteristics such as MAF overexpression per se. It is especially important to define risk status if HiR cases are to be managed appropriately because of their aggressive clinical course, high rates of early relapse and the need to maintain therapeutic pressure on the clone.

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Acknowledgements

This manuscript was supported by a grant from the National Institutes of Health (P01CA055819).

Author contributions

GJM and NW conceived and planned the project; AR, CS, AH and NW conducted statistical analyses; CH, ST and NW interpreted results; ET performed FISH analyses; patients were accrued by BB, CH, FD, FVVR, GJM, ST and MZ; all authors wrote and approved the manuscript.

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Authors and Affiliations

  1. Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    N Weinhold, C J Heuck, S Thanendrarajan, C K Stein, F Van Rhee, M Zangari, E Tian, F E Davies, B Barlogie & G J Morgan

  2. Cancer Research and Biostatistics, Seattle, WA, USA

    A Rosenthal & A Hoering

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  1. N Weinhold
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  2. C J Heuck
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  3. A Rosenthal
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  6. F Van Rhee
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  7. M Zangari
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  8. A Hoering
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  9. E Tian
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  10. F E Davies
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  11. B Barlogie
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  12. G J Morgan
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Corresponding author

Correspondence to G J Morgan.

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Competing interests

BB and CJH have received research funding from Celgene and Millennium. BB is a consultant to Celgene and Millennium and is a co-inventor on patents and patent applications related to the use of GEP in cancer medicine that have been licensed to Signal Genetics Inc. GJM has participated in advisory boards for, received payment for lectures and development of educational presentations from and has received travel support from Celgene, Novartis, Merck and Johnson & Johnson. FED has participated in advisory boards and spoken at meetings for Celgene, Ortho Biotech and Novartis and has received travel support to attend meetings from Celgene and Ortho Biotech. The remaining authors declare no conflict of interest.

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Weinhold, N., Heuck, C., Rosenthal, A. et al. Clinical value of molecular subtyping multiple myeloma using gene expression profiling. Leukemia 30, 423–430 (2016). https://doi.org/10.1038/leu.2015.309

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