title: Tyrosine kinase inhibitors as a first-line treatment in patients with newly diagnosed chronic myeloid leukemia in chronic phase: A mixed-treatment comparison.
abstract: Tyrosine kinase inhibitors (TKI) are the initial treatment for majority of newly diagnosed patients with chronic myelogenous leukemia (CML) in chronic phase (CP) and are associated with marked improvement in hematological, cytogenetic, molecular response and survival rates compared with other therapies. In this review, we summarize the evidence of TKI efficacy for patients with newly diagnosed CP-CML. Six trials at low risk of bias evaluating TKIs as an initial treatment in adults with newly diagnosed CP-CML and enrolling 2,456 patients were included. Follow-up times ranged from a median of 3 months to 5 years. Direct comparison showed statistically higher rates of major molecular response (MMR ≤ 0.1%(IS)) achievement with second-generation TKIs at 12 months which was sustained throughout treatment period. Bayesian mixed-treatment comparison (MTC) analysis demonstrated superiority of both nilotinib and dasatinib over imatinib in terms of efficacy. Nilotinib was associated with higher deeper molecular responses (MR(4.5) ≤ 0.0032%(IS)) at 60 months than dasatinib but no difference in MMR. The differences between nilotinib and dasatinib are likely clinically trivial. Among TKIs, nilotinib was found to have the best survival profile. Both nilotinib and dasatinib are associated with significantly better MMR compared to imatinib that is sustained over 60 months. This analysis shows that new-generation TKIs are not only showing faster response but also maintaining a more potent one through longer follow-up period. It is important to note out that MTC is not a substitute for well-conducted RCTs investigating direct comparisons.
authors.affiliation: University of Arkansas for Medical Sciences/Winthrop Rockefeller Cancer Institute, Little Rock, AR.|Ellis Fischel Cancer Center, University of Missouri, Columbia, MO.
authors.forename: Belal
authors.initials: B
authors.lastname: Firwana
authors.affiliation: Department of Medicine, Georgia Regents University, Augusta, GA.
authors.forename: Mohamad Bassam
authors.initials: MB
authors.lastname: Sonbol
authors.affiliation: Department of Medicine, Wayne State University, Detroit, MI.
authors.forename: Maria
authors.initials: M
authors.lastname: Diab
authors.affiliation: Ellis Fischel Cancer Center, University of Missouri, Columbia, MO.|Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center, New York, NY.
authors.forename: Shahzad
authors.initials: S
authors.lastname: Raza
authors.affiliation: Division of Endocrinology and Metabolism, University of Arkansas for Medical Sciences, Little Rock, AR.
authors.forename: Rim
authors.initials: R
authors.lastname: Hasan
authors.affiliation: Department of Medicine, Indiana University, Indianapolis, IN.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Yousef
authors.affiliation: Cleveland Clinic, Cleveland, OH.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Zarzour
authors.affiliation: Ellis Fischel Cancer Center, University of Missouri, Columbia, MO.
authors.forename: Archana
authors.initials: A
authors.lastname: Garipalli
authors.affiliation: Ellis Fischel Cancer Center, University of Missouri, Columbia, MO.
authors.forename: Donald
authors.initials: D
authors.lastname: Doll
authors.affiliation: Division of Preventive Medicine, Mayo Clinic, Rochester, MN.
authors.forename: M Hassan
authors.initials: MH
authors.lastname: Murad
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN.
authors.forename: Aref
authors.initials: A
authors.lastname: Al-Kali
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015466:Leukemia, Myeloid, Chronic-Phase / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors
keywords: BCR-ABL; chronic myelogenous leukemia; dasatinib; hematologic neoplasms; imatinib; nilotinib; tyrosine kinase inhibitor