TY - JOUR
T1 - Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib
AU - Mulligan, George
AU - Mitsiades, Constantine
AU - Bryant, Barb
AU - Zhan, Fenghuang
AU - Chng, Wee J.
AU - Roels, Steven
AU - Koenig, Erik
AU - Fergus, Andrew
AU - Huang, Yongsheng
AU - Richardson, Paul
AU - Trepicchio, William L.
AU - Broyl, Annemiek
AU - Sonneveld, Pieter
AU - Shaughnessy, John D.
AU - Bergsagel, P. Leif
AU - Schenkein, David
AU - Esseltine, Dixie Lee
AU - Boral, Anthony
AU - Anderson, Kenneth C.
PY - 2007/4/15
Y1 - 2007/4/15
N2 - The aims of this study were to assess the feasibility of prospective pharmacogenomics research in multicenter international clinical trials of bortezomib in multiple myeloma and to develop predictive classifiers of response and survival with bortezomib. Patients with relapsed myeloma enrolled in phase 2 and phase 3 clinical trials of bortezomib and consented to genomic analyses of pretreatment tumor samples. Bone marrow aspirates were subject to a negative-selection procedure to enrich for tumor cells, and these samples were used for gene expression profiling using DNA microarrays. Data quality and correlations with trial outcomes were assessed by multiple groups. Gene expression in this dataset was consistent with data published from a single-center study of newly diagnosed multiple myeloma. Response and survival classifiers were developed and shown to be significantly associated with outcome via testing on independent data. The survival classifier improved on the risk stratification provided by the International Staging System. Predictive models and biologic correlates of response show some specificity for bortezomib rather than dexamethasone. Informative gene expression data and genomic classifiers that predict clinical outcome can be derived from prospective clinical trials of new anticancer agents.
AB - The aims of this study were to assess the feasibility of prospective pharmacogenomics research in multicenter international clinical trials of bortezomib in multiple myeloma and to develop predictive classifiers of response and survival with bortezomib. Patients with relapsed myeloma enrolled in phase 2 and phase 3 clinical trials of bortezomib and consented to genomic analyses of pretreatment tumor samples. Bone marrow aspirates were subject to a negative-selection procedure to enrich for tumor cells, and these samples were used for gene expression profiling using DNA microarrays. Data quality and correlations with trial outcomes were assessed by multiple groups. Gene expression in this dataset was consistent with data published from a single-center study of newly diagnosed multiple myeloma. Response and survival classifiers were developed and shown to be significantly associated with outcome via testing on independent data. The survival classifier improved on the risk stratification provided by the International Staging System. Predictive models and biologic correlates of response show some specificity for bortezomib rather than dexamethasone. Informative gene expression data and genomic classifiers that predict clinical outcome can be derived from prospective clinical trials of new anticancer agents.
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U2 - 10.1182/blood-2006-09-044974
DO - 10.1182/blood-2006-09-044974
M3 - Article
C2 - 17185464
AN - SCOPUS:34147129816
SN - 0006-4971
VL - 109
SP - 3177
EP - 3188
JO - Blood
JF - Blood
IS - 8
ER -