Angiogenic factors could help us to define patients obtaining complete response with undetectable minimal residual disease in untreated CLL patients treated by FCR: results from the CLL2010FMP, a FILO study

Abstract

Angiogenesis is in a constant balance between pro and anti-angiogenic factors. Neoangiogenesis, implicated in metastatic spreading is characterized in solid cancers, but fairly new in chronic lymphocytic leukemia (CLL). We hypothesize that secretion of angiogenic factors could be correlated to the pathogenesis of CLL, and therefore predict the outcome of patients. We investigated concentrations of 22 cytokines and chemokines in 137 non-del 17p B-CLL patients, treated with a fludarabine-cyclophosphamide-rituximab (FCR)-based regimen. We constructed a biomarker index defining different risk groups based on lymphocyte count, the intensity of CD20 antigen on CD19⁺ cells, Ang-2, and PDGF-BB plasma concentrations at diagnosis. Four groups were defined, exhibiting specific molecular signatures and correlated with progression-free survival of patients. Our results suggest that we can determine at diagnosis of non-del 17p B-CLL patients, those with a very high probability of progression-free survival, independently of IGVH mutational status and residual disease at the end of treatment.

Keywords:

• Chronic lymphocytic leukemia
• angiogenesis
• molecular signature

Disclosure statement

Franciane Paul received support for attending meetings and/or travel from Roche and Servier and served on the advisory board/board for Novartis and Servier, Guillaume Cartron received consulting fees from Roche and celgene and received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Sanofi, Abbvie, Gilead, Jansen, Roche and BMS.

Additional information

Funding

This work was supported by the Agence Nationale de la Recherche (ANR-10-LABX-53-01), Fondation de l'Avenir pour la Recherche Médicale Appliquée (APRM-17001), F. Hoffman-La Roche Ltd (Translational research grant on ‘angiogenesis and tumors), GIRCI SOHO (API-K : 2011 043), GOELAMS, SILLC ‘Association de Soutien et d'Information à la Leucémie Lymphoïde Chronique et la maladie de Waldenström” and Groupement des Entreprises Françaises dans la lutte contre le Cancer.