ARTÍCULO

Response to lenalidomide in myelodysplastic syndromes with del(5q): influence of cytogenetics and mutations

Autores: Mallo, M.; Del Rey, M.; Ibáñez, M.; Calasanz Abinzano, María José; Arenilllas, L.; Larráyoz Ilundáin, María José; Pedro, C.; Jerez, A.; Maciejewski, J.; Costa, D.; Nomdedeu, M.; Diez-Campelo, M.; Lumbreras, E.; González-Martínez, T.; Marugán, I.; Such, E.; Cervera, J.; Cigudosa, J. C.; Álvarez, S.; Florensa, L.; Hernández, J. M.; Solé, F.
Título de la revista: BRITISH JOURNAL OF HAEMATOLOGY
ISSN: 0007-1048
Volumen: 162
Número: 1
Páginas: 74 - 86
Fecha de publicación: 2013
Resumen:
Lenalidomide is an effective drug in low-risk myelodysplastic syndromes (MDS) with isolated del(5q), although not all patients respond. Studies have suggested a role for TP53 mutations and karyotype complexity in disease progression and outcome. In order to assess the impact of complex karyotypes on treatment response and disease progression in 52 lenalidomide-treated patients with del(5q) MDS, conventional G-banding cytogenetics (CC), single nucleotide polymorphism array (SNP-A), and genomic sequencing methods were used. SNP-A analysis (with control sample, lymphocytes CD3+, in 30 cases) revealed 5q losses in all cases. Other recurrent abnormalities were infrequent and were not associated with lenalidomide responsiveness. Low karyotype complexity (by CC) and a high baseline platelet count (>280x109/l) were associated with the achievement of haematological response (P=0020, P=0013 respectively). Unmutated TP53 status showed a tendency for haematological response (P=0061). Complete cytogenetic response was not observed in any of the mutated TP53 cases. By multivariate analysis, the most important predictor for lenalidomide treatment failure was a platelet count <280x109/l (Odds Ratio=617, P=0040). This study reveals the importance of a low baseline platelet count, karyotypic complexity and TP53 mutational status for response to lenalidomide treatment. It supports the molecular study of TP53 in MDS patients treated with lenalidomide.