Abstract
BackgroundSeveral new drugs are approved for treatment of patients with multiple myeloma (MM), but no validated biomarkers are available for the prediction of a clinical outcome. We aimed to establish whether pretreatment blood and bone marrow plasma concentrations of major cytokines and angiogenic factors (CAFs) of patients from a phase 3 trial of a MM treatment could have a prognostic and predictive value in terms of response to therapy and progression-free and overall survival and whether these patients could be stratified for their prognosis.MethodsBlood and bone marrow plasma levels of Ang-2, FGF-2, HGF, VEGF, PDGF-β, IL-8, TNF-α, TIMP-1, and TIMP-2 were determined at diagnosis in MM patients enrolled in the GIMEMA MM0305 randomized controlled trial by an enzyme-linked immunosorbent assay (ELISA). These levels were correlated both reciprocally and with the type of therapy and patients’ characteristics and with a group of non-MM patients as controls.ResultsNo significant differences were detected between the blood and bone marrow plasma levels of angiogenic cytokines. A cutoff for each CAF was established. The therapeutic response of patients with blood plasma levels of CAFs lower than the cutoff was better than the response of those with higher levels in terms of percentage of responding patients and quality of response.ConclusionFGF-2, HGF, VEGF, and PDGF-β plasma levels at diagnosis have predictive significance for response to treatment. The stratification of patients based on the levels of CAFs at diagnosis and their variations after therapy is useful to characterize different risk groups concerning outcome and response to therapy.Trial registrationClinical trial information can be found at the following link: NCT01063179
Highlights
Several new drugs are approved for treatment of patients with multiple myeloma (MM), but no validated biomarkers are available for the prediction of a clinical outcome
We evaluated the concentration of ANG-2, fibroblast growth factor-2 (FGF-2), hepatocyte growth factor (HGF), IL-8, platelet-derived growth factor-BB (PDGF-BB), Tissue Inhibitor of Matrix Metalloproteinase (TIMP)-1, TIMP-2, Tumor Necrosis Factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF) that are the major cytokines involved in angiogenesis in MM and other cancers [36] and, as previously demonstrated [37] in MM patients, directly correlate with disease activity and increase with progression
Our results showed that there were no differences in the levels of the studied cytokines and angiogenic factors (CAFs) between the peripheral blood and bone marrow plasma samples of MM patients (Fig. 1, Additional file 1: Table S1), indicating that the concentrations of circulating cytokines well reflect those of the bone marrow and could be used for all subsequent analyses
Summary
Several new drugs are approved for treatment of patients with multiple myeloma (MM), but no validated biomarkers are available for the prediction of a clinical outcome. We aimed to establish whether pretreatment blood and bone marrow plasma concentrations of major cytokines and angiogenic factors (CAFs) of patients from a phase 3 trial of a MM treatment could have a prognostic and predictive value in terms of response to therapy and progression-free and overall survival and whether these patients could be stratified for their prognosis
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