Journal
BLOOD
Volume 126, Issue 17, Pages 1996-2004Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2015-05-644039
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Funding
- Center for Translational Molecular Medicine (BioCHIP)
- European Hematology Association
- Early-Mid Career Researchers Translational Research Grant
- Federal Ministry of Education and Research of Germany from CLIOMMICS (Clinically-applicable, omics-based assessment of survival, side effects, and targets in multiple myeloma) [01ZX1309A]
- SkylineDx
- Janssen Pharmaceuticals
- Myeloma Stem Cell Network (MSCNET) [LSHC-Ct-2006-037602]
- Medical Research Council [MR/L01629X/1] Funding Source: researchfish
- MRC [MR/L01629X/1] Funding Source: UKRI
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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.
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