title: Impact of Genetic Mutations and Health Plan Access to Therapies on Treatment Response and Drug Costs Related to Tyrosine Kinase Inhibitor Treatment Among Patients With Chronic Myelogenous Leukemia.
abstract: This study assessed treatment responses and economic consequences of limiting access to the second-generation BCR-ABL1 tyrosine kinase inhibitors (2G-TKI), dasatinib and nilotinib, for treatment of chronic myelogenous leukemia, while taking into account frequencies of genetic mutations that exhibit different sensitivities to the 2G-TKIs.
  
  
  
  Frequencies of BCR-ABL1 mutations and the impact of mutations on responses to 2G-TKIs were obtained from published literature and used as inputs in a decision analytics model. Complete hematologic response (CHR) and major cytogenetic response (MCyR) were estimated after 12 months of 2G-TKI treatment. Total annual 2G-TKI drug costs per CHR and MCyR were estimated and compared among 3 2G-TKI access scenarios: (1) open access to both 2G-TKIs; (2) access restricted to dasatinib (DASA-only); and (3) access restricted to nilotinib (NILO-only).
  
  
  
  Among a hypothetical cohort of 1000 2G-TKI-treated chronic myelogenous leukemia patients, the percentage of patients with CHR and MCyR were greatest for the open access plan (CHR: 93%, MCyR: 56%), followed by DASA-only (88%, 53%) and NILO-only (67%, 47%). Compared with the 2G-TKI costs per CHR in open access ($120,706/CHR), the costs were 5% higher ($126,753/CHR) in DASA-only and 41% higher ($169,990/CHR) in NILO-only. Likewise, compared with the 2G-TKI costs per MCyR in open access ($198,284/MCyR), the costs were 6% higher ($209,259/MCyR) in DASA-only and 22% higher ($241,515/MCyR) in NILO-only.
  
  
  
  Open access to both 2G-TKIs is associated with improved clinical and economic outcomes: greater treatment response rates (CHR and MCyR) and lower drug costs compared with restricted access to 2G-TKIs.
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.affiliation: Bristol-Myers Squibb, Princeton.
authors.forename: Dinara
authors.initials: D
authors.lastname: Makenbaeva
authors.affiliation: Novosys Health, Green Brook, NJ.
authors.forename: Melissa
authors.initials: M
authors.lastname: Lingohr-Smith
authors.affiliation: Novosys Health, Green Brook, NJ.
authors.forename: Jay
authors.initials: J
authors.lastname: Lin
mesh_terms: D000970:Antineoplastic Agents / Q000191:economics* / Q000627:therapeutic use*; D000069439:Dasatinib / Q000191:economics / Q000627:therapeutic use; D003661:Decision Support Techniques; D016527:Drug Costs; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006297:Health Services Accessibility; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000191:economics* / Q000235:genetics*; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000191:economics / Q000627:therapeutic use; D011743:Pyrimidines / Q000191:economics / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C581634:BCR-ABL1 fusion protein, human; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib; D000069439:Dasatinib