Abstract 1800 Introduction: Survival of patients with newly diagnosed multiple myeloma (MM) is highly variable and currently used clinical prognostic markers such as the international staging system (ISS) and cytogenetic markers are insufficiently adequate for defining individual patient prognosis. We established a prognostic signature based on gene expression profiling. Methods: The signature was generated using a training set of 290 newly diagnosed MM patients included in the multicenter, prospective open-label randomized phase 3 HOVON65/GMMG-HD4 trial. Gene expression profiles, obtained from purified plasma cells, were generated using the Affymetrix GeneChip® Human Genome U133 Plus 2.0 platform (GSE19784; Broyl et al.,Blood 2010; 14:2543–2553). The model predictive for survival was built by supervised principal component analysis (Bair et al., J. Amer. Statistical Assoc. 2006;101:119–37) and further optimized by simulated annealing. The generated survival signature was compared to six previously reported MM gene expression signatures (i.e. UAMS-70, UAMS-17 (Shaughnessy et al., Blood. 2007;109:2276–84), gene expression-based proliferation index (GPI, Hose et al., Haematol. 2010; 96: 87–95), MRC-IX-6 gene (Dickens et al., Clin. Cancer Res. 2010;16:1856–1864), Millennium (Mulligan et al., Blood 2007; 109:3177–3188) and IFM (Decaux et al., J. Clin. Oncol. 2008; 26:4798–4805). Results: A signature of 92 probe sets (EMC-92-gene signature) was highly discriminative for high-risk MM patients, defined as overall survival (OS) Conclusions: We developed a high-risk signature highly discriminative for patients with high-risk versus standard-risk MM, irrespective of treatment regime, age and relapse setting. Use of this signature in the clinical setting may lead to a more informed treatment choice and potentially better outcome for the patient. Disclosures: van Vliet:Skyline Diagnostics: Employment. van Beers:Skyline Diagnostics: Employment, Patents & Royalties. Mulligan:Millennium Pharmaceuticals, Inc.: Employment. Morgan:Millennium Pharmaceuticals, Inc: Honoraria. Gregory:Celgene: Honoraria. Goldschmidt:Johnson& Johnson: Membership on an entity9s Board of Directors or advisory committees. Lokhorst:Genmab: Membership on an entity9s Board of Directors or advisory committees; Celgene: Membership on an entity9s Board of Directors or advisory committees. Sonneveld:Janssen: Membership on an entity9s Board of Directors or advisory committees; Celgene: Membership on an entity9s Board of Directors or advisory committees; Skyline Diagnostics: Membership on an entity9s Board of Directors or advisory committees.
[1]
John Crowley,et al.
Pharmacogenomics of bortezomib test-dosing identifies hyperexpression of proteasome genes, especially PSMD4, as novel high-risk feature in myeloma treated with Total Therapy 3.
,
2011,
Blood.
[2]
Axel Benner,et al.
Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma
,
2011,
Haematologica.
[3]
P. Sonneveld,et al.
Gene expression profiling for molecular classification of multiple myeloma in newly diagnosed patients.
,
2010,
Blood.
[4]
Anthony Boral,et al.
Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib.
,
2006,
Blood.
[5]
Yongsheng Huang,et al.
A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1.
,
2006,
Blood.