Medical Costs of Adverse Events in Chronic Myeloid Leukemia Patients Treated with Tyrosine Kinase Inhibitors: Canadian Perspective.
Authors: Newton Nick , Ouagari Khalid El , Goetghebeur Mireille M. 
Published: October 2019

Abstract
Background: Imatinib (Gleevec) is recommended first-line therapy for treatment of chronic myeloid leukemia (CML). A relatively small group of patients treated with imatinib develop resistance or are intolerant to the treatment. Dose escalation of imatinib may be used in some cases. Recently, two treatment options, nilotinib (Tasigna) and dasatinib (Sprycel), have become possible alternatives for patients resistant or intolerant to imatinib. Current data indicates that nilotinib and dasatinib have a different side effect profile.
Objectives: This study investigated the costs of adverse events (AEs) in patients receiving nilotinib or dasatinib for chronic and accelerated CML.
Methods: Incidence rates of grade 3/4 AEs treated with nilotinib or dasatinib were obtained from nilotinib Phase II Summary of Clinical Safety: 120-Day Safety Update Report and dasatinib product information, respectively. Costs for non-hematological AEs were obtained from the Ontario Case Costing Initiative (OCCI) acute inpatient databases, using ICD-10 codes cross-referenced with AEs described in product monographs. For ICD 10 codes identified for this study, there were not enough cases in CML patients (a minimum of five cases is required to access data) and therefore OCCI costs used in this study were those of AEs in oncology patients. These costs were considered a good approximation of costs of AEs in CML patients by the clinical expert. Costs for grade 3 anemia and thrombocytopenia, and non-febrile neutropenia, were assumed to be outpatient costs and were based on literature, expert validation of treatment pathways and resource utilization in the Canadian context. Costs for grade 4 anemia and thrombocytopenia, and febrile neutropenia, were obtained from the OCCI. Multivariate sensitivity analyses were conducted on costs of AEs. The analysis was developed from a payer perspective considering direct medical costs only. Costs are reported in 2006 Canadian dollars.
Results: Cost of treatment-related AEs for CML patients was higher for dasatinib than nilotinib. For both treatments, total costs for AEs associated with the accelerated phase were higher than those associated with the chronic phase: $19,902 versus $7,653 for dasatinib; $8,645 versus $3,790 for nilotinib; respectively. Cost attributable to hematological AEs represented between 45% and 71% of total cost of AEs. Ranking observed among treatments for base case costs of AEs was maintained for both high and low cost estimates, indicating that the model was robust to variation in cost of AEs.
Conclusions: For patients resistant or intolerant to imatinib, costs of dasatinib-related AEs were approximately twice the costs of nilotinib-related AEs in both chronic and accelerated phases, highlighting the importance of considering the cost of AEs in economic evaluation of new tyrosine kinase inhibitors. Further research is needed to comprehensively evaluate the impact of AEs on healthcare expenditures.