title: Evaluation of Long-Term Chronic Myeloid Leukemia Treatment Practices with Tyrosine Kinase Inhibitors in a National Cohort of Veterans.
abstract: To evaluate nationwide chronic myeloid leukemia (CML) treatment practices over an extended period and across multiple lines of tyrosine kinase inhibitor (TKI) therapy with imatinib, dasatinib, and nilotinib.
  
  
  
  Retrospective cohort study.
  
  
  
  Veterans Health Administration (VHA) national database.
  
  
  
  A total of 2873 VHA beneficiaries aged 18-89 years who had at least one encounter at any of the ~150 VHA hospitals and 800 VHA clinics, had a diagnosis code for CML, and filled at least one prescription for imatinib, nilotinib, or dasatinib between October 1, 2001, and September 30, 2010.
  
  
  
  The VHA database was used for the time period of October 1, 2000, to September 30, 2012, allowing for a 1-year observation period to identify CML treatments prior to study enrollment and a minimum of a 2-year follow-up period to assess study end points. Primary study end points included change in TKI treatment, gaps in TKI treatment, TKI treatment persistence, and patient survival. Persistence for each distinct line of treatment was defined as the time of continuous therapy, quantified by the number of days covered by the drug from treatment initiation until a 60-day gap in treatment was identified or a switch in treatment occurred. A Kaplan-Meier model was used to evaluate persistence and survival. Of the 2873 patients receiving first-line TKI treatment, 586 (20.4%) switched to a different TKI, constituting second-line treatment. Overall, 245 patients (8.5%) were switched again to third-line treatment. Only 4.4% of patients receiving first-line treatment experienced a gap in therapy of 60 or more days. First-line treatment persistence rates were 75%, 65%, and 55% for the first, second, and third years of treatment, respectively. Five-year survival with first-line treatment was 62%.
  
  
  
  In this national cohort of VHA patients, 1-year persistence of first-line TKI treatment was similar to that in prior studies. Five-year survival was comparable with that in other observational studies but was lower than that in prospective clinical trials. Persistence rates declined after the introduction of the new TKIs.
authors.affiliation: Clinical and Administrative Sciences, College of Pharmacy, California Northstate University, Elk Grove, California.
authors.forename: Eugene D
authors.initials: ED
authors.lastname: Kreys
authors.affiliation: Pharmacotherapy Division, College of Pharmacy, The University of Texas at Austin, Austin, Texas.|Pharmacotherapy Education and Research Center, School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, Texas.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Frei
authors.affiliation: Pharmacotherapy Division, College of Pharmacy, The University of Texas at Austin, Austin, Texas.|Pharmacotherapy Education and Research Center, School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, Texas.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Villarreal
authors.affiliation: South Texas Veterans Health Care System, San Antonio, Texas.
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Bollinger
authors.affiliation: South Texas Veterans Health Care System, San Antonio, Texas.
authors.forename: Xavier
authors.initials: X
authors.lastname: Jones
authors.affiliation: Pharmacotherapy Division, College of Pharmacy, The University of Texas at Austin, Austin, Texas.|Pharmacotherapy Education and Research Center, School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, Texas.
authors.forename: Jim M
authors.initials: JM
authors.lastname: Koeller
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015331:Cohort Studies; D000069439:Dasatinib / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate / Q000494:pharmacology / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors; D014481:United States; D014493:United States Department of Veterans Affairs; D014728:Veterans; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; C498826:nilotinib; D000069439:Dasatinib
keywords: chronic myeloid leukemia; long term; survival; treatment persistence; tyrosine kinase inhibitors; veterans