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A novel panel of protein biomarkers for predicting response to thalidomide‐based therapy in newly diagnosed multiple myeloma patients
Author(s) -
Rajpal Rajesh,
Dowling Paul,
Meiller Justine,
Clarke Colin,
Murphy William G.,
O'Connor Robert,
Kell Malcolm,
Mitsiades Constantine,
Richardson Paul,
Anderson Kenneth C.,
Clynes Martin,
O'Gorman Peter
Publication year - 2011
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201000471
Subject(s) - thalidomide , multiple myeloma , oncology , medicine , myeloma protein
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.