Cost impact of Bruton's tyrosine kinase inhibitor selection in Medicare patients with chronic lymphocytic leukemia.

To estimate cost savings associated with covalent Bruton's tyrosine kinase inhibitor (cBTKi) choice in patients with treatment-naive (TN) and relapsed/refractory (RR) chronic lymphocytic leukemia (CLL) from a Medicare perspective. An economic model with Markov structure simulated outcomes in patients with CLL initiating ibrutinib, acalabrutinib or zanubrutinib monotherapy. Modeled population included TN and RR patients who had no prior cBTKi. Treatments were dosed per US FDA label and efficacy assumed identical across cBTKis. Cumulative grade ≥3 adverse event (AE) rates were drawn from extended follow-up of cBTKi phase III clinical trials at similar duration. Costs included drug price per 2024 wholesale acquisition cost and AE management medical costs from literature, adjusted for Medicare reimbursement. Outcomes were total change in payer cost over 1, 3 and 5 years. A cohort of 13,726 patients with CLL was modeled (44% TN, 56% RR). Acalabrutinib's aggregate grade ≥3 AE rate was 25.8% points less in TN patients (35.8% vs 61.6%) and 8.0% points less in RR patients (75.0% vs 83.0%) compared with ibrutinib, and 20.6% points less in TN patients (35.8% vs 56.4%) and 11.1% points less in RR patients (75.0% vs 86.1%) compared with zanubrutinib. Acalabrutinib saved $15,478 more per patient versus ibrutinib in year 1 due to lower treatment cost (-$12,076) and lower AE cost (-$3402). Acalabrutinib also saved $1901 more per patient versus zanubrutinib as acalabrutinib higher treatment cost (+$1663) was offset by lower AE cost (-$3563). Across all patients, acalabrutinib saved $212 million more versus ibrutinib and $26 million more versus zanubrutinib from a Medicare perspective. Acalabrutinib cost savings persisted over 3 and 5 years. Acalabrutinib yielded cost savings versus ibrutinib and zanubrutinib for patients with CLL in Medicare due to lower treatment cost versus ibrutinib and fewer grade ≥3 AEs versus both ibrutinib and zanubrutinib.