Dasatinib early intervention after cytogenetic or hematologic resistance to imatinib in patients with chronic myeloid leukemia.
BACKGROUND
Although many patients with chronic myeloid leukemia (CML) respond well to imatinib therapy, a significant proportion loses their initial response. Loss of response on imatinib is often because of BCR-ABL mutations. Dasatinib is a 325-fold more potent inhibitor of Bcr-Abl than imatinib and has been associated with high rates of durable responses in patients with CML in chronic phase (CP) after imatinib failure.


METHODS
To determine the optimal time for initiating dasatinib after loss of response on imatinib, data from dasatinib trials in CML-CP were analyzed. Patients were grouped according to whether they received early intervention with dasatinib (ie, after cytogenetic recurrence on imatinib), rather than after both cytogenetic and hematologic recurrence.


RESULTS
Overall, 72% of patients who received dasatinib after loss of a major cytogenetic response (MCyR) on imatinib achieved a complete cytogenetic response (CCyR) compared with 42% of patients who were treated after loss of both MCyR and complete hematologic response (CHR). Event-free survival (EFS) also was higher after earlier dasatinib treatment (24-month EFS rates: 89% after loss of MCyR on imatinib vs 29% after loss of both MCyR and CHR). Among patients who were treated after loss of CHR on imatinib with no prior MCyR, 26% achieved a CCyR with dasatinib, and the 24-month EFS rate was 64%. In all 3 groups, CCyR rates were similar in patients with or without pre-existing BCR-ABL mutations.


CONCLUSIONS
The results of the current study suggested that optimal outcomes are achieved when dasatinib is administered early after imatinib resistance.
Quintás-Cardama
Alfonso
A
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
Cortes
Jorge E
JE
O'Brien
Susan
S
Ravandi
Farhad
F
Borthakur
Gautam
G
Liu
David
D
Bleickardt
Eric
E
Chen
Tai-Tsang
TT
Kantarjian
Hagop M
HM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D001772:Blood Cell Count; D000069439:Dasatinib; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D013844:Thiazoles / Q000008:administration & dosage*; D013997:Time Factors; D055815:Young Adult
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib