Dasatinib in the treatment of chronic myeloid leukemia in accelerated phase after imatinib failure: the START a trial.
PURPOSE Patients with chronic myelogenous leukemia in accelerated phase (CML-AP) that is resistant or intolerant to imatinib have limited therapeutic options. Dasatinib, a potent inhibitor of BCR-ABL and SRC-family kinases, has efficacy in patients with CML-AP who have experienced treatment failure with imatinib. We now report follow-up data from the full patient cohort of 174 patients enrolled onto a phase II trial to provide a more complete assessment of the efficacy and safety of dasatinib in this population. PATIENTS AND METHODS Patients with imatinib-resistant (n = 161) or -intolerant (n = 13) CML-AP received dasatinib 70 mg orally twice daily. Results At a median follow-up of 14.1 months (treatment duration, 0.1 to 21.7 months), major and complete hematologic responses were attained by 64% and 45% of patients, respectively, and major and complete cytogenetic responses were achieved in 39% and 32% of patients, respectively. Responses were achieved irrespective of imatinib status (resistant or intolerant), prior stem-cell transplantation, or the presence of prior BCR-ABL mutation. The 12-month progression-free survival and overall survival rates were 66% and 82%, respectively. Dasatinib was generally well tolerated; the most frequent nonhematologic severe treatment-related adverse event was diarrhea (52%; grade 3 to 4, 8%). Cytopenias were common, including grade 3 to 4 neutropenia (76%) and thrombocytopenia (82%). Pleural effusion occurred in 27% of patients (grade 3 to 4, 5%). CONCLUSION Dasatinib is effective in patients with CML-AP after imatinib treatment failure.
Apperley
Jane F
JF
Hammersmith Hospital, Imperial College School of Medicine, Du Cane Rd, London W12 0NN, United Kingdom. j.apperley@imperial.ac.uk
Cortes
Jorge E
JE
Kim
Dong-Wook
DW
Roy
Lydia
L
Roboz
Gail J
GJ
Rosti
Gianantonio
G
Bullorsky
Eduardo O
EO
Abruzzese
Elisabetta
E
Hochhaus
Andreas
A
Heim
Dominik
D
de Souza
Carmino A
CA
Larson
Richard A
RA
Lipton
Jeffrey H
JH
Khoury
H Jean
HJ
Kim
Hyeoung-Joon
HJ
Sillaber
Christian
C
Hughes
Timothy P
TP
Erben
Philipp
P
Van Tornout
Jan
J
Stone
Richard M
RM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D000069439:Dasatinib; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011743:Pyrimidines / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D000069439:Dasatinib