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

Ilaria Saltarella, Fortunato Morabito, Nicola Giuliani, Carolina Terragna, Paola Omedè, Antonio Palumbo, Sara Bringhen, Lorenzo De Paoli, Enrica Martino, Alessandra Larocca, Massimo Offidani, Francesca Patriarca, Chiara Nozzoli, Tommasina Guglielmelli, Giulia Benevolo, Vincenzo Callea, Luca Baldini, Mariella Grasso, Giovanna Leonardi, Manuela RizzoAntonietta Pia Falcone, Daniela Gottardi, Vittorio Montefusco, Pellegrino Musto, Maria Teresa Petrucci, Franco Dammacco, Mario Boccadoro, Angelo Vacca, Roberto Ria

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number4
JournalJournal of Hematology and Oncology
Issue number1
Publication statusPublished - Jan 9 2019


  • Angiogenic factors
  • Multiple myeloma
  • Overall survival
  • Progression-free survival
  • Response rate

ASJC Scopus subject areas

  • Hematology
  • Molecular Biology
  • Oncology
  • Cancer Research

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