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Myeloma

A novel prognostic model in myeloma based on co-segregating adverse FISH lesions and the ISS: analysis of patients treated in the MRC Myeloma IX trial

Leukemia volume 26, pages 349–355 (2012)Cite this article

Abstract

The association of genetic lesions detected by fluorescence in situ hybridization (FISH) with survival was analyzed in 1069 patients with newly presenting myeloma treated in the Medical Research Council Myeloma IX trial, with the aim of identifying patients associated with the worst prognosis. A comprehensive FISH panel was performed, and the lesions associated with short progression-free survival and overall survival (OS) in multivariate analysis were +1q21, del(17p13) and an adverse immunoglobulin heavy chain gene (IGH) translocation group incorporating t(4;14), t(14;16) and t(14;20). These lesions frequently co-segregated, and there was an association between the accumulation of these adverse FISH lesions and a progressive impairment of survival. This observation was used to define a series of risk groups based on number of adverse lesions. Taking this approach, we defined a favorable risk group by the absence of adverse genetic lesions, an intermediate group with one adverse lesion and a high-risk group defined by the co-segregation of >1 adverse lesion. This genetic grouping was independent of the International Staging System (ISS) and so was integrated with the ISS to identify an ultra-high-risk group defined by ISS II or III and >1 adverse lesion. This group constituted 13.8% of patients and was associated with a median OS of 19.4 months.

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Acknowledgements

Main financial support for the Myeloma IX clinical trial was from UK Medical Research Council, with additional funding in the form of unrestricted educational grants from Novartis, Schering Health Care, Chugai, Pharmion, Celgene and Ortho Biotech. The LLR UKMF Cytogenetics group received financial support from Leukaemia and Lymphoma Research. The Institute of Cancer Research received support from Myeloma UK, Cancer Research UK and the biological research center of the National Institute for Health Research at the Royal Marsden Hospital. The University of Leeds acted as the trial sponsor. We acknowledge the support of the National Institute for Health Research, through the National Cancer Research Network. We thank Rebecca Protheroe, David Stockley, Tim Parker, Hazel Robinson, Elisabet Dachs Cabanas and Christina Rudduck of the LLR UKMF Cytogenetics group for probe preparation and FISH scoring. We also thank staff from the Clinical Trials Research Unit, University of Leeds, for trial co-ordination and data management.

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Authors and Affiliations

  1. Division of Molecular Pathology, The Institute of Cancer Research, Surrey, UK

    K D Boyd, B A Walker, C P Wardell, F E Davies & G J Morgan

  2. Wessex Regional Genetics Laboratory, University of Southampton, Salisbury, UK

    F M Ross, L Chiecchio, G P Dagrada, Z J Konn & W J Tapper

  3. Clinical Trials Research Unit, University of Leeds, Leeds, UK

    W M Gregory, A J Szubert, S E Bell & J A Child

  4. Haematology Department, University of Newcastle, Newcastle-upon-Tyne, UK

    G H Jackson

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  1. K D Boyd
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Correspondence to G J Morgan.

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Author contributions

GJM, JAC and GHJ were chief investigators of the MRC Myeloma IX trial. KDB, BAW, CPW and GJM designed research, analyzed data and wrote the paper. JAC, GHJ and FED designed research and wrote the paper. FMR designed research, performed research, analyzed data and wrote the paper. LC, GPD and ZJC performed research. WMG, AJS, SEB and WJT analyzed data.

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Boyd, K., Ross, F., Chiecchio, L. et al. A novel prognostic model in myeloma based on co-segregating adverse FISH lesions and the ISS: analysis of patients treated in the MRC Myeloma IX trial. Leukemia 26, 349–355 (2012). https://doi.org/10.1038/leu.2011.204

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