title: Early responses predict better outcomes in patients with newly diagnosed chronic myeloid leukemia: results with four tyrosine kinase inhibitor modalities.
abstract: Early responses to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML)-chronic phase (CP) are associated with improved outcome. We analyzed the impact of such a response on outcomes among patients treated with 4 TKI modalities as frontline therapy in CML-CP. A total of 483 patients who received 400 or 800 mg imatinib, nilotinib, or dasatinib were analyzed. The median follow-up was 72 mo. Landmark analysis at 3 mo by molecular response showed that the cumulative proportions of 3-y event-free survival (EFS) for 3-mo BCR-ABL levels was 95% for those with ≤1%, 98% for >1% to 10%, and 61% for those with >10% (P = .001). The corresponding values by cytogenetic responses were 97% if Ph+ = 0%, 89% if Ph+ = 1% to 35%, and 81% if Ph+ >35% (P = .001). Cytogenetic response at 3 mo significantly discriminated for 3-y overall survival (OS): 98%, 96%, and 92%, respectively (P = .01). In multivariate analysis, young patients, high Sokal index, and treatment with imatinib 400 significantly predicted for poor (>35%) cytogenetic response at 3 mo. Early responses are predictive for EFS and failure-free survival and to a lesser extent OS, regardless of the treatment modality, although therapies other than standard-dose imatinib result in higher rates of deep early responses.
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Preetesh
authors.initials: P
authors.lastname: Jain
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Aziz
authors.initials: A
authors.lastname: Nazha
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Carlos Guillermo
authors.initials: CG
authors.lastname: Romo
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
authors.forename: Marylou
authors.initials: M
authors.lastname: Cardenas-Turanzas
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Alfonso
authors.initials: A
authors.lastname: Quintás-Cardama
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides / Q000008:administration & dosage*; D000069439:Dasatinib; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D015996:Survival Rate; D013844:Thiazoles / Q000008:administration & dosage*
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; C498826:nilotinib; D000069439:Dasatinib