Prediction of high- and low-risk multiple myeloma based on gene expression and the International Staging System.
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.
Department of Hematology, Erasmus Medical Center Cancer Institute, Rotterdam, The Netherlands;
Rowan
R
Kuiper
Department of Hematology, Erasmus Medical Center Cancer Institute, Rotterdam, The Netherlands;
Mark
M
van Duin
SkylineDx, Erasmus Medical Center Cancer Institute, Rotterdam, The Netherlands;
Martin H
MH
van Vliet
Department of Hematology, Erasmus Medical Center Cancer Institute, Rotterdam, The Netherlands;
Annemiek
A
Broijl
Hemato-Oncologie voor Volwassenen Nederland Data Center, Erasmus Medical Center Cancer Institute-Clinical Trial Center, Rotterdam, The Netherlands;
Bronno
B
van der Holt
Hemato-Oncologie voor Volwassenen Nederland Data Center, Erasmus Medical Center Cancer Institute-Clinical Trial Center, Rotterdam, The Netherlands;
Laila
L
El Jarari
SkylineDx, Erasmus Medical Center Cancer Institute, Rotterdam, The Netherlands;
Erik H
EH
van Beers
Millennium Pharmaceuticals, Cambridge, MA;
George
G
Mulligan
Unité de Génomique du Myélome, Centre Hospitalier Universitaire Rangueil, Toulouse, France;
Hervé
H
Avet-Loiseau
Clinical Trials Research Unit, University of Leeds, Leeds, United Kingdom;
Walter M
WM
Gregory
Royal Marsden Hospital, London, United Kingdom;
Gareth
G
Morgan
University of Heidelberg, Heidelberg, Germany; and.
Hartmut
H
Goldschmidt
Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
Henk M
HM
Lokhorst
Department of Hematology, Erasmus Medical Center Cancer Institute, Rotterdam, The Netherlands;
Pieter
P
Sonneveld
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002869:Chromosome Aberrations; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007390:International Agencies; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D009101:Multiple Myeloma / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate
D014408:Biomarkers, Tumor