title: 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.
abstract: 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.
authors.affiliation: Leukemia Department, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Constantine S
authors.initials: CS
authors.lastname: Tam
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Jenny
authors.initials: J
authors.lastname: Shan
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
mesh_terms: 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
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; C498826:nilotinib; D000069439:Dasatinib