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Blood. 2015 Oct 22;126(17):1996-2004. doi: 10.1182/blood-2015-05-644039. Epub 2015 Sep 1.

Prediction of high- and low-risk multiple myeloma based on gene expression and the International Staging System.

Author information

1
Department of Hematology, Erasmus Medical Center Cancer Institute, Rotterdam, The Netherlands;
2
SkylineDx, Erasmus Medical Center Cancer Institute, Rotterdam, The Netherlands;
3
Hemato-Oncologie voor Volwassenen Nederland Data Center, Erasmus Medical Center Cancer Institute-Clinical Trial Center, Rotterdam, The Netherlands;
4
Millennium Pharmaceuticals, Cambridge, MA;
5
Unité de Génomique du Myélome, Centre Hospitalier Universitaire Rangueil, Toulouse, France;
6
Clinical Trials Research Unit, University of Leeds, Leeds, United Kingdom;
7
Royal Marsden Hospital, London, United Kingdom;
8
University of Heidelberg, Heidelberg, Germany; and.
9
Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.

Abstract

Patients with multiple myeloma have variable survival and require reliable prognostic and predictive scoring systems. Currently, clinical and biological risk markers are used independently. Here, International Staging System (ISS), fluorescence in situ hybridization (FISH) markers, and gene expression (GEP) classifiers were combined to identify novel risk classifications in a discovery/validation setting. We used the datasets of the Dutch-Belgium Hemato-Oncology Group and German-speaking Myeloma Multicenter Group (HO65/GMMG-HD4), University of Arkansas for Medical Sciences-TT2 (UAMS-TT2), UAMS-TT3, Medical Research Council-IX, Assessment of Proteasome Inhibition for Extending Remissions, and Intergroupe Francophone du Myelome (IFM-G) (total number of patients: 4750). Twenty risk markers were evaluated, including t(4;14) and deletion of 17p (FISH), EMC92, and UAMS70 (GEP classifiers), and ISS. The novel risk classifications demonstrated that ISS is a valuable partner to GEP classifiers and FISH. Ranking all novel and existing risk classifications showed that the EMC92-ISS combination is the strongest predictor for overall survival, resulting in a 4-group risk classification. The median survival was 24 months for the highest risk group, 47 and 61 months for the intermediate risk groups, and the median was not reached after 96 months for the lowest risk group. The EMC92-ISS classification is a novel prognostic tool, based on biological and clinical parameters, which is superior to current markers and offers a robust, clinically relevant 4-group model.

PMID:
26330243
PMCID:
PMC4616233
DOI:
10.1182/blood-2015-05-644039
[Indexed for MEDLINE]
Free PMC Article

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