Response to lenalidomide in myelodysplastic syndromes with del(5q): influence of cytogenetics and mutations
Mar Mallo, Mónica Del Rey, Mariam Ibáñez, M José Calasanz, Leonor Arenillas, M José Larráyoz, Carmen Pedro, Andrés Jerez, Jaroslaw Maciejewski, Dolors Costa, Meritxell Nomdedeu, María Diez-Campelo, Eva Lumbreras, Teresa González-Martínez, Isabel Marugán, Esperanza Such, José Cervera, Juan C Cigudosa, Sara Alvarez, Lourdes Florensa, Jesús M Hernández, Francesc Solé, Mar Mallo, Mónica Del Rey, Mariam Ibáñez, M José Calasanz, Leonor Arenillas, M José Larráyoz, Carmen Pedro, Andrés Jerez, Jaroslaw Maciejewski, Dolors Costa, Meritxell Nomdedeu, María Diez-Campelo, Eva Lumbreras, Teresa González-Martínez, Isabel Marugán, Esperanza Such, José Cervera, Juan C Cigudosa, Sara Alvarez, Lourdes Florensa, Jesús M Hernández, Francesc Solé
Abstract
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 (>280 × 10(9) /l) were associated with the achievement of haematological response (P = 0·020, P = 0·013 respectively). Unmutated TP53 status showed a tendency for haematological response (P = 0·061). 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 <280 × 10(9) /l (Odds Ratio = 6·17, P = 0·040). 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.
© 2013 John Wiley & Sons Ltd.
Source: PubMed