Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome.
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.
Avet-Loiseau
Hervé
H
INSERM Unité 601, Laboratoire d'Hématologie, Institut de Biologie, 9 quai Moncousu, 44093 Nantes, France. herve.avetloiseau@chu-nantes.fr
Attal
Michel
M
Moreau
Philippe
P
Charbonnel
Catherine
C
Garban
Frédéric
F
Hulin
Cyrille
C
Leyvraz
Serge
S
Michallet
Mauricette
M
Yakoub-Agha
Ibrahim
I
Garderet
Laurent
L
Marit
Gérald
G
Michaux
Lucienne
L
Voillat
Laurent
L
Renaud
Marc
M
Grosbois
Bernard
B
Guillerm
Gaelle
G
Benboubker
Lotfi
L
Monconduit
Mathieu
M
Thieblemont
Catherine
C
Casassus
Philippe
P
Caillot
Denis
D
Stoppa
Anne-Marie
AM
Sotto
Jean-Jacques
JJ
Wetterwald
Marc
M
Dumontet
Charles
C
Fuzibet
Jean-Gabriel
JG
Azais
Isabelle
I
Dorvaux
Véronique
V
Zandecki
Marc
M
Bataille
Régis
R
Minvielle
Stéphane
S
Harousseau
Jean-Luc
JL
Facon
Thierry
T
Mathiot
Claire
C
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005602:France; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009101:Multiple Myeloma / Q000235:genetics* / Q000401:mortality*; D009367:Neoplasm Staging; D011446:Prospective Studies; D015996:Survival Rate