Dataset Information

Prognostic or predictive value of circulating cytokines and angiogenic factors for initial treatment of multiple myeloma in the GIMEMA MM0305 randomized controlled trial.

ABSTRACT:

Background

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.

Methods

Blood 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.

Results

No 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.

Conclusion

FGF-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 registration

Clinical trial information can be found at the following link: NCT01063179.

SUBMITTER: Saltarella I

PROVIDER: S-EPMC6327520 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Publications

Prognostic or predictive value of circulating cytokines and angiogenic factors for initial treatment of multiple myeloma in the GIMEMA MM0305 randomized controlled trial.

Saltarella Ilaria I Morabito Fortunato F Giuliani Nicola N Terragna Carolina C Omedè Paola P Palumbo Antonio A Bringhen Sara S De Paoli Lorenzo L Martino Enrica E Larocca Alessandra A Offidani Massimo M Patriarca Francesca F Nozzoli Chiara C Guglielmelli Tommasina T Benevolo Giulia G Callea Vincenzo V Baldini Luca L Grasso Mariella M Leonardi Giovanna G Rizzo Manuela M Falcone Antonietta Pia AP Gottardi Daniela D Montefusco Vittorio V Musto Pellegrino P Petrucci Maria Teresa MT Dammacco Franco F Boccadoro Mario M Vacca Angelo A Ria Roberto R

Journal of hematology & oncology 20190109 1

<h4>Background</h4>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 wh ...[more]

PMID: 30626425

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Project description:BackgroundCirculating angiogenic cytokines (CACs) have been confirmed as prognostic biomarkers and therapeutic targets in several solid tumors. However, their role as prognostic biomarkers in resected pancreatic ductal adenocarcinoma (PDAC) is unknown.ResultsThe expression of CACs in patients with PDAC differs from those with CP both pre- and postoperatively. Correlation analyses show significant correlations between circulating levels of CACs: VEGF was correlated with IL-6 (r = 0.457), FGF (r = 0.44), G-CSF (r = 0.543), HGF (r = 0.586) and SDF-1α (r = 0.784) before the surgery. The circulating levels of TNF-α correlated with the serum concentration of IL-4 before (r= 0.656) and after the resection (r = 0.776 on POD 3, r = 0.865 on POD 7). Gender did not show any correlation with serum levels of CAC, except for significantly higher levels of EGF in males (P = 0.002). Other clinicopathological variables such as age (< 65 vs. > 65 years), T, N, or UICC stage did not have an association with the cytokine levels. The multivariate model including the entire angiogenic panel revealed that postoperative increasing levels of EGF (P = 0.023), PDGFA-A (P = 0.024), TNF-α (P = 0.001) and IL-8 (P = 0.049) were associated with a favorable prognosis, whereas elevating levels of VEGF (P = 0.005) correlated with a poor cancer-specific survival.Materials and methodsPreoperative and postoperative blood samples were collected in patients undergoing surgery for PDAC (n = 40) or chronic pancreatitis (CP; n = 9). Serum levels of 13 angiogenic cytokines (IL-4, IL-6, FGF-b, G-CSF, TNF-α, VEGF, HGF, SDF-1α, IL-8, EGF, Ang-1, PDGF-AA and PlGF) were analyzed using ELISA and Multiplex. Prognostic factors were identified by a Cox proportional hazards model.ConclusionsPostoperative changes of serum levels of certain angiogenic cytokines correlate with patients' prognosis after resection for pancreatic cancer. CACs should thus be considered as biomarkers in patients with resected pancreatic cancer.

Dataset Information

Prognostic or predictive value of circulating cytokines and angiogenic factors for initial treatment of multiple myeloma in the GIMEMA MM0305 randomized controlled trial.

Background

Methods

Results

Conclusion

Trial registration

Publications

Prognostic or predictive value of circulating cytokines and angiogenic factors for initial treatment of multiple myeloma in the GIMEMA MM0305 randomized controlled trial.

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