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Response to lenalidomide in myelodysplastic syndromes with del(5q): influence of cytogenetics and mutations
Author(s) -
Mallo Mar,
del Rey Mónica,
Ibáñez Mariam,
Calasanz Mª José,
Arenillas Leonor,
Larráyoz Mª José,
Pedro Carmen,
Jerez Andrés,
Maciejewski Jaroslaw,
Costa Dolors,
Nomdedeu Meritxell,
DiezCampelo María,
Lumbreras Eva,
GonzálezMartínez Teresa,
Marugán Isabel,
Such Esperanza,
Cervera José,
Cigudosa Juan C.,
Álvarez Sara,
Florensa Lourdes,
Hernández Jesús Mª,
Solé Francesc
Publication year - 2013
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12354
Subject(s) - lenalidomide , myelodysplastic syndromes , cytogenetics , medicine , oncology , hematology , biology , multiple myeloma , bone marrow , genetics , chromosome , gene
Summary 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 TP 53 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 CD 3+, 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 TP 53 status showed a tendency for haematological response ( P = 0·061). Complete cytogenetic response was not observed in any of the mutated TP 53 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 TP 53 mutational status for response to lenalidomide treatment. It supports the molecular study of TP 53 in MDS patients treated with lenalidomide.