Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome
Hervé Avet-Loiseau, Michel Attal, Philippe Moreau, Catherine Charbonnel, Frédéric Garban, Cyrille Hulin, Serge Leyvraz, Mauricette Michallet, Ibrahim Yakoub-Agha, Laurent Garderet, Gérald Marit, Lucienne Michaux, Laurent Voillat, Marc Renaud, Bernard Grosbois, Gaelle Guillerm, Lotfi Benboubker, Mathieu Monconduit, Catherine Thieblemont, Philippe Casassus, Denis Caillot, Anne-Marie Stoppa, Jean-Jacques Sotto, Marc Wetterwald, Charles Dumontet, Jean-Gabriel Fuzibet, Isabelle Azais, Véronique Dorvaux, Marc Zandecki, Régis Bataille, Stéphane Minvielle, Jean-Luc Harousseau, Thierry Facon, Claire Mathiot, Hervé Avet-Loiseau, Michel Attal, Philippe Moreau, Catherine Charbonnel, Frédéric Garban, Cyrille Hulin, Serge Leyvraz, Mauricette Michallet, Ibrahim Yakoub-Agha, Laurent Garderet, Gérald Marit, Lucienne Michaux, Laurent Voillat, Marc Renaud, Bernard Grosbois, Gaelle Guillerm, Lotfi Benboubker, Mathieu Monconduit, Catherine Thieblemont, Philippe Casassus, Denis Caillot, Anne-Marie Stoppa, Jean-Jacques Sotto, Marc Wetterwald, Charles Dumontet, Jean-Gabriel Fuzibet, Isabelle Azais, Véronique Dorvaux, Marc Zandecki, Régis Bataille, Stéphane Minvielle, Jean-Luc Harousseau, Thierry Facon, Claire Mathiot
Abstract
Acquired genomic aberrations have been shown to significantly impact survival in several hematologic malignancies. We analyzed the prognostic value of the most frequent chromosomal changes in a large series of patients with newly diagnosed symptomatic myeloma prospectively enrolled in homogeneous therapeutic trials. All the 1064 patients enrolled in the IFM99 trials conducted by the Intergroupe Francophone du Myélome benefited from an interphase fluorescence in situ hybridization analysis performed on purified bone marrow plasma cells. They were systematically screened for the following genomic aberrations: del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p). Chromosomal changes were observed in 90% of the patients. The del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p) were present in 48%, 21%, 14%, 39%, 13%, and 11% of the patients, respectively. After a median follow-up of 41 months, univariate statistical analyses revealed that del(13), t(4;14), nonhyperdiploidy, and del(17p) negatively impacted both the event-free survival and the overall survival, whereas t(11;14) and MYC translocations did not influence the prognosis. Multivariate analyses on 513 patients annotated for all the parameters showed that only t(4;14) and del(17p) retained prognostic value for both the event-free and overall survivals. When compared with the currently used International Staging System, this prognostic model compares favorably. In myeloma, the genomic aberrations t(4;14) and del(17p), together with beta2-microglobulin level, are important independent predictors of survival. These findings have implications for the design of risk-adapted treatment strategies.
Source: PubMed