Efficacy and safety of dasatinib in imatinib-resistant or -intolerant patients with chronic myeloid leukemia in blast phase.
Dasatinib is an inhibitor of BCR-ABL and SRC-family kinases for patients with imatinib-resistant or -intolerant chronic myelogenous leukemia (CML). In this international phase II trial, dasatinib was administered orally (70 mg twice daily) to patients with myeloid blast phase (MBP, n=109) or lymphoid blast phase (LBP, n=48) CML. After a minimum follow-up of 12 months (range 0.03-20.7 months), major hematologic responses were induced in 34% (MBP-CML) and 35% (LBP-CML) of patients. Major cytogenetic responses were attained in 33% (MBP-CML) and 52% (LBP-CML) of patients and complete cytogenetic responses were attained in 26 and 46%, respectively. Median progression-free survival was 6.7 (MBP-CML) and 3.0 (LBP-CML) months. Median overall survival was 11.8 (MBP-CML) and 5.3 (LBP-CML) months. Overall, dasatinib had acceptable tolerability. Fluid retention events were more frequent in the MBP-CML than the LBP-CML cohort: pleural effusion occurred in 36 and 13% (all grades) and 15 and 6% (grades 3/4), respectively. Other non-hematologic side effects were primarily grade 1/2; grade 3/4 events were recorded in <or=6% of patients, except febrile neutropenia (15%). Cytopenias were noted in the majority of patients, and were manageable with dose interruptions/reductions. Dasatinib is associated with a promising rate of response in this high-risk population.
Cortes
J
J
Department of Leukemia, MD Anderson Cancer Center, Houston, TX, USA. jcortes@mdanderson.org
Kim
D-W
DW
Raffoux
E
E
Martinelli
G
G
Ritchie
E
E
Roy
L
L
Coutre
S
S
Corm
S
S
Hamerschlak
N
N
Tang
J-L
JL
Hochhaus
A
A
Khoury
H J
HJ
Brümmendorf
T H
TH
Michallet
M
M
Rege-Cambrin
G
G
Gambacorti-Passerini
C
C
Radich
J P
JP
Ernst
T
T
Zhu
C
C
Van Tornout
J M A
JM
Talpaz
M
M