Budget impact of fixed duration acalabrutinib in combination with venetoclax in previously untreated chronic lymphocytic leukemia patients in the United States Free

INTRODUCTION: Chronic lymphocytic leukemia (CLL) has seen significant therapeutic advances with targeted Bruton's tyrosine kinase (BTKi) and B-cell leukemia/lymphoma 2 (BCL2i) inhibitors. CLL treatments include treat-to-progression (TTP) therapy with BTKi as well as fixed-duration (FD) combination regimens. While TTP therapy offers oral dosing with minimal monitoring, it can lead to long-term healthcare costs. FD regimens require more intensive initial monitoring but offer patients the possibility of treatment-free intervals possibly lasting multiple years. Research shows patients with CLL would prefer FD over TTP therapy—assuming equal efficacy—due to the appeal of treatment-free periods. Acalabrutinib-venetoclax (AV), a second-generation BTKi+BCL2i combination, represents an advancement in FD therapy. AV demonstrated superior progression-free survival (p=0.004) and overall survival <0.001) compared to chemoimmunotherapy (CIT) in the AMPLIFY phase III trial, but the impact of the introduction of this regimen on health care costs is unknown. This study evaluated how introduction of AV for previously untreated patients with CLL would impact US patient-level and health plan costs, factors increasingly relevant to clinical decision-making in an era of value-based care.

METHODS: A budget impact model was developed from the US payer perspective over a 5-year time horizon (2025-2029). The model included standard of care (SoC) therapies for first-line CLL including single-agent TTP BTKis (ibrutinib, acalabrutinib, zanubrutinib), acalabrutinib-obinutuzumab, venetoclax-obinutuzumab, and CIT regimens. The analysis evaluated the introduction of AV at two levels: at the individual patient level and a health plan level. Comparison scenarios included (1) 100% use of AV versus 100% use of TTP BTKi for an individual patient, and (2) changes in CLL cost for a health plan across all indicated treatments assuming a gradual uptake of AV over time. The model estimated the annual number of eligible patients in the plan with previously untreated, symptomatic CLL eligible to start treatment based on US epidemiological data. Clinical inputs included treatment duration, adverse event (AE) rates, dosing, and treatment schedules, drawn from clinical trials. Cost inputs included drug acquisition, drug administration and tumor lysis syndrome monitoring, AE management, and disease management costs, inflated to 2025 USD.

RESULTS: A shift from TTP BTKi therapy to AV for individual patients with CLL (scenario 1) would result in a cumulative cost decrease of $618,849 per patient based on 5-year time to progression or next treatment. Year-over-year cost differences show an initial increase of $160,757 in year 1, followed by reduced cost of $184,254 in year 2 as the patient completes the 12.9-month FD AV therapy. Cost decreases in years 3-5 were $198,451 annually, as drug acquisition and disease management costsare eliminated after FD treatment completion, whereas TTP BTKi would continue to accrue these costs over time. In the typical US plan with 1-million-members, 37 patients were estimated to have CLL and eligible to initiate treatment in 2025. Examining the full treatment landscape with gradual AV uptake (scenario 2), introduction of AV was associated with cumulative cost reduction of $19,539 per incident diagnosed CLL patient in the health plan across the 5 years, corresponding to a decrease in monthly cost to the health plan (independent of profits and administrative costs) of $0.06 per health plan member per month and $722,943 lower total cumulative cost for the whole health plan.

CONCLUSIONS: Introduction of patient-preferred FD AV for previously untreated patients with CLL can help improve the long-run financial sustainability of the healthcare system. While associated with a short-run budget increase in year 1, the FD regimen ultimately reduced 5-year per-patient and health plan costs compared to TTP therapy, improving affordability of cancer care. This evidence on the economic impact of AV—alongside its clinical profile—can inform clinical decision-making and help payers and providers optimize treatment strategies for CLL.