Type

Journal Article

Authors

Peter O'Gorman
Martin Clynes
Kenneth C Anderson
Paul Richardson
Constantine Mitsiades
Malcolm Kell
Robert O'Connor
William G Murphy
Colin Clarke
Justine Meiller
and 2 others

Subjects

Microbiology

Topics
adverse effects administration dosage middle aged multiple myeloma aged humans treatment outcome tumor markers biological female therapeutic use enzyme linked immunosorbent assay drug therapy prognosis aged 80 and over gene expression profiling blood male thalidomide mass spectrometry sensitivity and specificity

A novel panel of protein biomarkers for predicting response to thalidomide-based therapy in newly diagnosed multiple myeloma patients. (2010)

Abstract Multiple myeloma (MM) is a heterogeneous group of disorders both genotypically and phenotypically. Response to thalidomide-based induction therapy in newly diagnosed patients varies significantly in published clinical trials. Proteomic analysis was performed on 39 newly diagnosed MM patients treated with a thalidomide-based regimen (22 responders; 17 non-responders) using immunodepletion, 2-D DIGE analysis and mass spectrometry. Zinc-α-2-glycoprotein (ZAG), vitamin D-binding protein (VDB), serum amyloid-A protein (SAA) and β-2-microglobulin (B2M) had statistically significant higher concentrations in non-responders compared to responders, while haptoglobin (Hp) had a lower concentration. ELISAs were used to validate the candidate protein biomarkers using unfractionated serum from 51 newly diagnosed MM patients (29 responders; 22 non-responders). Using logistic regression, the best possible area under the curve (AUC) was 0.96 using ZAG, VDB and SAA in combination. Leave-one-out-cross-validation (LOOCV) indicated an overall predictive accuracy of 84% with associated sensitivity and specificity values of 81.8 and 86.2%, respectively. Subsequently, 16 of 22 thalidomide-refractory patients successfully achieved complete response or very good partial response using second-line treatment suggesting that the biomarker profile is specific to thalidomide response rather than identifying patients with MM refractory to all therapies. Using a novel panel of predictive biomarkers, the feasibility of predicting response to thalidomide-based therapy in previously untreated MM has been demonstrated.
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Full list of authors on original publication

Peter O'Gorman, Martin Clynes, Kenneth C Anderson, Paul Richardson, Constantine Mitsiades, Malcolm Kell, Robert O'Connor, William G Murphy, Colin Clarke, Justine Meiller and 2 others

Experts in our system

1
Peter O'Gorman
Dublin City University
Total Publications: 15
 
2
Martin Clynes
Dublin City University
Total Publications: 209
 
3
Kenneth Anderson
Dublin City University
Total Publications: 5
 
4
Paul Richardson
Dublin City University
Total Publications: 6
 
5
Robert O'Connor
Dublin City University
Total Publications: 71
 
6
Colin Clarke
Dublin City University
Total Publications: 26
 
7
Justine Meiller
Dublin City University
Total Publications: 7