Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib.
Dasatinib, a potent inhibitor of BCR-ABL in vitro, is effective for patients with chronic myelogenous leukemia (CML) resistant or intolerant to imatinib. To provide a more definitive assessment of dasatinib in chronic-phase (CP)-CML, we report extended follow-up of a phase II trial, presenting data for the entire patient cohort (N=387). Dasatinib (70 mg) twice daily was administered to patients with imatinib-resistant or -intolerant CP-CML. With median follow-up of 15.2 months (treatment duration, <1-18.4 months), a complete hematologic response was attained or maintained in 91% of patients. A major cytogenetic response (MCyR) was attained or maintained by 59% (52% imatinib resistant and 80% imatinib intolerant); this was complete in 49% of patients (40% imatinib resistant and 75% imatinib intolerant). Of 230 patients achieving an MCyR, 7 experienced disease progression. Fifteen-month progression-free survival was 90% while overall survival was 96%. Grade 3/4 thrombocytopenia and neutropenia were reported in 48 and 49% of patients, respectively. Non-hematologic toxicity (any grade) consisted primarily of diarrhea (37%), headache (32%), fatigue (31%), dyspnea (30%) and pleural effusion (27%). Pleural effusions were classified as grade 3 in 6% of reported events, with no incidence of grade 4. Dasatinib is associated with high response rates in patients with imatinib-resistant or -intolerant CP-CML.
Hochhaus
A
A
III Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany. hochhaus@uni-hd.de
Baccarani
M
M
Deininger
M
M
Apperley
J F
JF
Lipton
J H
JH
Goldberg
S L
SL
Corm
S
S
Shah
N P
NP
Cervantes
F
F
Silver
R T
RT
Niederwieser
D
D
Stone
R M
RM
Dombret
H
H
Larson
R A
RA
Roy
L
L
Hughes
T
T
Müller
M C
MC
Ezzeddine
R
R
Countouriotis
A M
AM
Kantarjian
H M
HM
D000328:Adult; D000368:Aged; D001549:Benzamides; D000069439:Dasatinib; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000627:therapeutic use*; D015996:Survival Rate; D013844:Thiazoles / Q000627:therapeutic use*; D016896:Treatment Outcome
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib