Cost-Offset Analysis Performed Utilizing Covalent Bruton's Tyrosine Kinase Inhibitors Safety Profiles Among Medicare Patients with Chronic Lymphocytic Leukemia
Authors: Kittai Adam S , Patel Dipen A. , Shafrin Jason , Zawadzki Nadine , Shetty Vikram , Sharma Khounish , Barqawi Yazan K. , Rhodes Joanna M. 
Published: December 2024

INTRODUCTION: Chronic lymphocytic leukemia (CLL) has had a number of recent clinical advancements including FDA-approved covalent Bruton's tyrosine kinase inhibitors (cBKTis) ibrutinib, acalabrutinib, and zanubrutinib. While cBTKis demonstrate similar efficacy, acalabrutinib has shown lower rates of toxicity compared to ibrutinib in randomized clinical trials (RCTs) and zanubrutinib in matching-adjusted indirect comparisons (MAICs). Given the importance of mitigating the high cost of cancer-care, it is important to assess cost of different treatments, especially when multiple drugs are approved for the same indication. Thus, we performed a cost-offset analysis utilizing cBTKi safety profiles among Medicare patients with CLL. Findings of this analysis will estimate potential cost-savings associated with choice of cBTKi across prevalent treatment naïve (TN) and relapsed refractory (RR) CLL Medicare population from a Centers for Medicare & Medicaid Services (CMS) payer perspective.
METHODS: An economic model was constructed to simulate health and economic outcomes among patients with both TN and RR patients with CLL treated with cBTKi. A Markov model approach simulated transitions between 4 treatment pathway health states: cBTKi, venetoclax + rituximab, subsequent treatment (pooled pirtobrutinib, CAR T, and best supportive care), and death. Cumulative grade ≥3 adverse event (AE) rates for cBTKis were obtained from extended follow-up data of phase III RCTs to ensure similar follow-up duration. Treatments were dosed according to FDA labels and efficacy was assumed to be identical across cBTKi. Drug prices were based on 2024 wholesale acquisition costs (WACs). Medical costs associated with treatment of AEs used Medicare reimbursement rates. Outcomes were total change in cost from cBTKis treatment choice over a 1-year time period. Subgroup analysis examined outcomes for CLL patients in CMS special subpopulations (disabled, end-stage renal disease (ESRD), terminally ill). Sensitivity analyses included using MAIC results to inform AE rates and examining 3 and 5-year time horizons.
RESULTS: A cohort of 18,474 CLL patients was modeled (74% TN, 26% RR) to reflect real-world prevalence in Medicare. Annual WACs for acalabrutinib, ibrutinib, and zanubrutinib were $186,979, $213,677, and $183,303, respectively. Acalabrutinib showed cost savings of $16,919 per Medicare patient ($313 million across all Medicare patients with CLL) vs. ibrutinib over 1 year since treatment initiation, driven by lower treatment cost ($12,224 decrease) and lower AE cost ($4,695 decrease). Differences in AE costs were driven by differences in unadjusted rates of grade ≥3 atrial fibrillation (1.1% acalabrutinib vs. 5.2% ibrutinib), hypertension (2.8% vs. 8.1%), and infections (16.2% vs. 20.6%) in TN, and hypertension (4% vs. 9%), diarrhea (1% vs. 5%) and neutropenia (20% vs. 23%) in RR. Compared to zanubrutinib, acalabrutinib showed cost savings of $2,529 per patient ($47 million across all Medicare patients with CLL). Higher acalabrutinib treatment cost vs. zanubrutinib ($1,683 increase) was offset by savings from lower AE cost ($4,212 decrease). Differences in AE costs were driven by differences in hypertension and infections in TN (2.8% acalabrutinib vs. 9.2% zanubrutinib; 16.2% vs. 23.8%) and hypertension and infections in RR (4.0% vs. 16.4%; 31.0% vs. 35.5%). Sensitivity analysis using MAIC AE rates similarly showed overall cost savings per patient vs. ibrutinib ($16,209 decrease) and vs. zanubrutinib ($300 decrease) over 1 year. Acalabrutinib treatment of disabled, ESRD, and terminally ill Medicare CLL patients was associated with reduced grade ≥3 AEs vs. ibrutinib (2,640, 180, and 527 fewer, respectively) and vs. zanubrutinib (2,120, 152, and 451 fewer). Acalabrutinib showed cost savings of $187 million, $13 million, and $42 million vs. ibrutinib, and $31 million, $2.1 million, and $6.3 million vs. zanubrutinib across disabled, ESRD, and terminally ill, respectively. Overall cost savings per CLL patient vs. ibrutinib and zanubrutinib were maintained over 3 ($25,615; $1,331) and 5 ($27,635; $1,053) year horizons.
CONCLUSIONS: Acalabrutinib yielded cost savings compared to ibrutinib and zanubrutinib for Medicare patients with CLL due to lower treatment cost (ibrutinib) and fewer AEs (both ibrutinib and zanubrutinib). Findings were consistent across sub-groups and sensitivity analyses.