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Correlation between eight-gene expression profiling and response to therapy of newly diagnosed multiple myeloma patients treated with thalidomide–dexamethasone incorporated into double autologous transplantation

2013; Springer Science+Business Media; Volume: 92; Issue: 9 Linguagem: Inglês

10.1007/s00277-013-1757-6

1432-0584

Carolina Terragna, Matteo Renzulli, Daniel Remondini, Enrico Tagliafico, Francesco Di Raimondo, Francesca Patriarca, Giovanni Martinelli, Enrica Roncaglia, Luciano Masini, Patrizia Tosi, Elena Zamagni, Paola Tacchetti, A Ledda, Annamaria Brioli, Emanuele Angelucci, Nicoletta Testoni, Giulia Marzocchi, Piero Galieni, Alessandro Gozzetti, Marina Martello, Flores Dico, Katia Mancuso, Michèle Cavo,

PI3K/AKT/mTOR signaling in cancer

We performed a molecular study aimed at identifying a gene expression profile (GEP) signature predictive of attainment of at least near complete response (CR) to thalidomide–dexamethasone (TD) as induction regimen in preparation for double autologous stem cell transplantation in 112 younger patients with newly diagnosed multiple myeloma. A GEP supervised analysis was performed on a training set of 32 patients, allowing to identify 157 probe sets differentially expressed in patients with CR versus those failing CR to TD. We then generated an eight-gene GEP signature whose performance was subsequently validated in a training set of 80 patients. A correct prediction of response to TD was found in 71 % of the cases analyzed. The eight genes were downregulated in patients who achieved CR to TD. Comparisons between post-autotransplantation outcomes of the 44 non-CR-predicted patients and of the 36 CR-predicted patients showed that this latter subgroup had a statistically significant benefit in terms of higher rate of CR after autotransplant(s) and longer time to progression, event-free survival, and overall survival. These results can be an important first step to identify at diagnosis those patients who will respond more favourably to a particular treatment strategy.