Cost-effectiveness analysis of second-line tyrosine kinase inhibitor treatment for chronic myelogenous leukemia

Abstract

Aim:

A cost-effectiveness analysis was performed for sequential treatments of chronic myelogenous leukemia (CML) with tyrosine kinase inhibitors (TKIs) after failure of 1st line imatinib, from a commercial payer perspective in the US.

Methods:

A Markov model was developed to simulate lifetime treatment costs and health outcomes for TKI sequences for treatment of patients resistant or intolerant to 1st-line imatinib. Five health states were included, chronic phase 2nd-line TKI, chronic phase 3rd-line TKI, chronic phase post-TKI, advanced phases, and death. Efficacy (response achievement, loss of response, transformation, death) and safety (adverse events incidence, discontinuation) data are based on clinical trials. Resource utilization, costs, and utilities were based on product labels and publically available data. Uncertainty analyses were conducted for key inputs.

Results:

In patients failing imatinib, dasatinib-initiating treatment sequences provide the most survival (ΔLYs = 0.2–2.0), QALYs (ΔQALYs = 0.2–1.9), and accrue highest CML-related costs (ΔCosts = $64,000–$222,000). The average ICER per QALY for dasatinib- vs imatinib-initiating sequences is $100,000 for an imatinib-resistant population. The average ICER per QALY for dasatinib- vs nilotinib-initiating sequences is $170,000 for an imatinib-resistant population, and $160,000 for an imatinib-intolerant population.

Conclusions:

This analysis suggests that dasatinib is associated with increased survival and quality of life compared to high dose imatinib and to a smaller extent with nilotinib, among patients resistant or intolerant to 1st-line imatinib, primarily based on higher cytogenetic response rates observed in clinical studies of dasatinib. Head-to-head studies of sequential use of dasatinib and nilotinib are needed to validate the model findings of improved survival (LYs) with better quality-of-life (QALYs) for patients initiating dasatinib in 2nd-line. However, the model findings (in light of higher cytogenetic response rates with dasatinib) are supported by other studies showing improved quality-of-life for responders, and improved survival for patients achieving cytogenetic response.

Keywords::

• Chronic myelogenous leukemia
• TKI
• Cost-effectiveness analysis
• Economic analysis
• Dasatinib

Transparency

Declaration of funding

Funding for this study and development of this manuscript was provided by Bristol-Myers Squibb.

Declaration of financial/other relationships

JW, IS, and AA are employees of Evidera, which has received research funds from Bristol-Myers Squibb in connection with conducting this study and development of this manuscript. EF, DM, and BB are employees of Bristol-Myers Squibb and own stock in the company. JME peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgement

The cost-effectiveness model was developed by Evidera, Inc. (Evidera). Evidera (Lexington, USA) was contracted by Bristol-Myers Squibb to produce the economic models, analysis and manuscript. The authors would like to thank research scientist, statisticians, cost specialists at Evidera and colleagues at Bristol-Myers Squibb for their valuable insight.