Abstract
To assess the impact of BCR-ABL kinase domain mutations on dasatinib response in elderly chronic myeloid leukemia (CML) patients, we analyzed the outcome of 76 individuals aged >60 affected by imatinib-resistant chronic-phase CML. We found that 36 cases (47 %) displayed mutations before dasatinib. Compared to non-mutated patients, subjects with point mutations had a worse response to dasatinib, with significantly lower rates of complete cytogenetic response (57 vs 32 %), higher percentage of primary resistance (16/36 vs 6/40) and a trend towards a shorter median event-free survival. Our data suggest that, in elderly patients, detection of BCR-ABL mutations negatively affects response to dasatinib.
MeSH terms
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Aged
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Antineoplastic Agents / adverse effects
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use*
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Benzamides
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DNA Mutational Analysis
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Dasatinib
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Disease-Free Survival
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Drug Resistance, Neoplasm / genetics*
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Female
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Fusion Proteins, bcr-abl / genetics
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Fusion Proteins, bcr-abl / physiology*
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Humans
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Imatinib Mesylate
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Italy / epidemiology
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Kaplan-Meier Estimate
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Leukemia, Myeloid, Chronic-Phase / drug therapy*
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Leukemia, Myeloid, Chronic-Phase / enzymology
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Leukemia, Myeloid, Chronic-Phase / genetics
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Leukemia, Myeloid, Chronic-Phase / mortality
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Male
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Middle Aged
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Mutation, Missense*
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Piperazines / adverse effects
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Piperazines / pharmacology*
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Point Mutation*
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Protein Kinase Inhibitors / adverse effects
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Protein Kinase Inhibitors / pharmacology
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Protein Kinase Inhibitors / therapeutic use*
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Pyrimidines / adverse effects
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Pyrimidines / pharmacology*
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Pyrimidines / therapeutic use*
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Retrospective Studies
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Thiazoles / adverse effects
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Thiazoles / pharmacology
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Thiazoles / therapeutic use*
Substances
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Antineoplastic Agents
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Benzamides
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Piperazines
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Protein Kinase Inhibitors
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Pyrimidines
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Thiazoles
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Imatinib Mesylate
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Fusion Proteins, bcr-abl
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Dasatinib