Impact of BCR-ABL mutations on response to dasatinib after imatinib failure in elderly patients with chronic-phase chronic myeloid leukemia.
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.
Division of Hematology and Bone Marrow Transplantation, Azienda Ospedialiero-Universitaria, Piazzale S. M. Misericordia 15, Udine, Italy. mario.tiribelli@uniud.it
Mario
M
Tiribelli
Roberto
R
Latagliata
Luigiana
L
Luciano
Fausto
F
Castagnetti
Antonella
A
Gozzini
Giovanna Rege
GR
Cambrin
Mario
M
Annunziata
Fabio
F
Stagno
Patrizia
P
Pregno
Francesco
F
Albano
Elisabetta
E
Abruzzese
Pellegrino
P
Musto
Enrico
E
Montefusco
Carmen
C
Fava
Renato
R
Fanin
Fabrizio
F
Pane
Gianantonio
G
Rosti
Massimo
M
Breccia
Giuliana
G
Alimena
Paolo
P
Vigneri
D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001549:Benzamides; D004252:DNA Mutational Analysis; D000069439:Dasatinib; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000502:physiology*; D006801:Humans; D000068877:Imatinib Mesylate; D007558:Italy / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010879:Piperazines / Q000009:adverse effects / Q000494:pharmacology*; D017354:Point Mutation; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D012189:Retrospective Studies; D013844:Thiazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib