Maximizing the Value of Chronic Myeloid Leukemia Management Using Tyrosine Kinase Inhibitors in the USA: Potential Determinants and Consequences of Healthcare Resource Utilization and Costs, with Proposed Optimization Approaches.

Background and objectives: The introduction and widespread use of effective and well-tolerated tyrosine kinase inhibitors for chronic myeloid leukemia have been associated with marked increments in life expectancy and disease prevalence. These changes have been accompanied by elevations in costs of tyrosine kinase inhibitors, which typically must be taken ad vitam after diagnosis and tend to be more expensive than medical therapies for many other hematologic malignancies. The aims of this review included evaluating the potential associations and consequences of healthcare resource utilization and costs of tyrosine kinase inhibitors and possible clinical management approaches to mitigate them.

Methods: A PubMed search of English-language US study reports was conducted that covered the interval of 2001 (US approval of imatinib) through 17 April, 2023 augmented by manual reviews of published bibliographies from the referenced articles and searches of other databases: Google Scholar and Scopus.

Results: On the basis of this analysis of chiefly real-world evidence (administrative claims database studies), healthcare resource utilization and costs can be considered indicators of ineffective chronic myeloid leukemia management, including potentially mutation-driven treatment resistance and costly tyrosine kinase inhibitor switches, non-adherence, and suboptimal tolerability, which may culminate in the progression of disease from the chronic to an accelerated or blast phase, with additional excess costs. Costs of tyrosine kinase inhibitors are also associated with reduced treatment adherence. At a willingness-to-pay threshold of $50,000-$200,000 per quality-adjusted life-year, tyrosine kinase inhibitors can be considered cost effective from a US payer perspective. Potential clinical approaches to mitigate costs include regular molecular monitoring with proactive assessments of BCR::ABL1 gene mutations to avoid costly treatment switches, as well as interventions to enhance treatment adherence and tyrosine kinase inhibitor tolerability.

Conclusions: Healthcare resource utilization and costs of chronic myeloid leukemia care may be considered barometers of ineffective management, including mutation-driven tyrosine kinase inhibitor resistance and switching as well as non-adherence and intolerance. Future prospective research is warranted to help determine whether costs can be reduced and other treatment outcomes optimized via more proactive and effective diagnostic interventions (i.e., regular molecular monitoring and proactive mutational testing) and treatment approaches. The strengths and limitations of this review include its emphasis on observational research, which, on one hand, offers a naturalistic "real-world" perspective on current chronic myeloid leukemia management, but, on the other hand, is associational in nature and cannot be used to determine causality and/or its direction.