Clinical and pharmacoeconomic analysis of first- and second-line therapy with Bruton tyrosine kinase inhibitors for chronic lymphocytic leukemia in KazakhstanND-LINE THERAPY WITH BRUTON TYROSINE KINASE INHIBITORS FOR CHRONIC LYMPHOCYTIC LEUKEMIA IN KAZAKHSTAN

Abstract

Relevance: Bruton tyrosine kinase inhibitors (BTKis) have significantly improved outcomes in chronic lymphocytic leukemia (CLL), but their high cost and differing safety profiles warrant pharmacoeconomic evaluation.

The study aimed to compare the costs and effectiveness of long-term acalabrutinib versus ibrutinib therapy in first-line and second-line CLL in Kazakhstan and to assess the budget impact of treatment choice.

Methods: A cost-effectiveness analysis was conducted using a three-state semi-Markov model (progression-free, progressed disease, death) over a 20-year horizon for first-line and a 10-year horizon for second-line. Efficacy inputs were derived from key trials (ELEVATE-TN, RESONATE-2, ELEVATE-RR). Direct medical costs included drug costs (2024 prices) and management of adverse events (AEs). Effectiveness was measured in quality-adjusted life years (QALYs), accounting for utility loss from serious AEs. Sensitivity analyses and a budget impact analysis were performed.

Results: In the base case, acalabrutinib and ibrutinib had equivalent anti-leukemic efficacy (median PFS ~8–9 years in 1st line; 38.4 months in 2nd line; no difference in OS). Due to a more favorable safety profile, acalabrutinib yielded higher QALYs than ibrutinib: +0.48 QALY per patient in the first line and +0.13 QALY in the second line. Total pre-progression costs per patient were lower with acalabrutinib by KZT 3.08 million (–0.93%) in the first line and KZT 1.54 million (–1.16%) in the second line, mainly due to reduced AE management costs. Incremental analysis indicated that acalabrutinib dominates ibrutinib (greater QALYs at lower cost), with cost savings of KZT 6.40–11.85 million per QALY gained. Expanding acalabrutinib use to 85% of high-risk patients (TP53 mutation/17p deletion) could reduce total budget expenditure by ~0.23% over 3 years.

Conclusions: The semi-Markov model results showed that acalabrutinib and ibrutinib are equally effective in treating patients. However, the acalabrutinib strategy is better because it costs less overall and yields a higher QALY, driven by lower side-effect management costs. These findings support the rationale for broader use of acalabrutinib, particularly in high-risk patients, to optimize outcomes and resource utilization.