Failure to achieve a major cytogenetic response by 12 months defines inadequate response in patients receiving nilotinib or dasatinib as second or subsequent line therapy for chronic myeloid leukemia.
To determine when patients with incomplete responses on second-line tyrosine kinase inhibitor (2TKI) therapy should consider alternative treatment, we analyzed the outcome of 113 patients receiving nilotinib (n = 43) or dasatinib (n = 70) after imatinib failure. After 12 months of 2TKI therapy, patients achieving a major cytogenetic response (12MMCyR) had a significant survival advantage over patients in minor cytogenetic response or complete hematologic response, with a projected one-year survival of 97% and 84% respectively (P = .02). Projected 1-year progression to hematologic failure, accelerated phase, or blast phase was also significantly different (3% vs 17%, P = .003). Early cytogenetic response was strongly predictive of achievement of 12MMCyR, with less than 10% of patients showing no cytogenetic response at 3 to 6 months eventually attaining the target of 12MMCyR. These results suggest that patients receiving 2TKI with no cytogenetic response at 3 to 6 months should be considered for alternative therapies.
Tam
Constantine S
CS
Leukemia Department, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Kantarjian
Hagop
H
Garcia-Manero
Guillermo
G
Borthakur
Gautam
G
O'Brien
Susan
S
Ravandi
Farhad
F
Shan
Jenny
J
Cortes
Jorge
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D020732:Cytogenetic Analysis; D000069439:Dasatinib; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D010879:Piperazines; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage*; D012074:Remission Induction; D016019:Survival Analysis; D013844:Thiazoles / Q000008:administration & dosage*; D017211:Treatment Failure
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; C498826:nilotinib; D000069439:Dasatinib