ABSTRACT
BACKGROUND: Following approval of imatinib, a breakthrough tyrosine kinase inhibitor (TKI), survival significantly improved by more than 20% since 2001 among treated chronic myelogenous leukemia (CML) patients. Subsequently, more expensive second-generation TKIs with varying selectivity profiles have been approved. Population-based studies are needed to evaluate the real-world utilization of TKI therapies, particularly given their escalating costs and recommendations for maintenance therapy. OBJECTIVE: To assess the utilization patterns of first-line TKIs, overall and by specific agent, among elderly CML patients in the United States, and the cost implications. METHODS: CML patients aged 65 years and older at diagnosis between 2007 and 2015 were identified from population-based cancer registries in the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. The percentage of CML patients receiving imatinib, dasatinib, or nilotinib within the first year of diagnosis was calculated along with time to first-line treatment initiation. Bivariate comparisons and Cox proportional hazards models were used to identify factors associated with TKI initiation. Average monthly patient responsibility, including patient out-of-pocket (OOP) costs, stratified by Part D low-income subsidy (LIS) status were also calculated. RESULTS: Among the 1,589 CML patients included, receipt of any TKI within 1 year of diagnosis increased from 66.2% to 78.9%. In 2015, the distribution of first-line TKI therapies was 41.3% imatinib, 28.3% dasatinib, and 9.3% nilotinib. Almost 60% of patients initiated TKI treatment within 3 months of diagnosis. Multivariable analysis indicated that TKI use in the first year was lower among the very elderly (aged > 75 years vs. 65-69 years: HR = 0.72; 95% CI = 0.63-0.83), patients with more comorbidities (Hierarchical Condition Category risk score > 2 vs. HR = 0.74, 95% CI = 0.62-0.88), and patients ineligible for LIS (HR = 0.75; 95% CI = 0.65-0.87). Average monthly patient OOP cost was significantly lower for LIS-eligible versus LIS-ineligible patients: imatinib (2016: $12 vs. $487), dasatinib (2016: $34 vs. $557), and nilotinib (2016: $1 vs. $526). CONCLUSIONS: TKI use has increased significantly since 2007. While imatinib remained the most frequently prescribed first-line agent, by 2015 newer TKIs represented one third of the market share. Utilization patterns indicated persistent age, comorbidity, and financial barriers. TKI use is indicated for long-term therapy, and increased adoption of newer, more expensive agents raises concerns about the sustained affordability of CML treatment, particularly among unsubsidized patients. DISCLOSURES: No outside funding supported this study. There are no reported conflicts of interest.
