Estimated total cost of care and patient out-of-pocket cost savings with first-line fixed duration venetoclax + obinutuzumab compared with treat-to-progression BTKi regimens among Medicare-eligible patients with chronic lymphocytic leukemia in the United States following the Inflation Reduction Act.

Abstract Background: In a recently published United States (US) population model of patients with previously untreated chronic lymphocytic leukemia (CLL), venetoclax — the only US Food and Drug Administration-approved B-cell lymphoma 2 inhibitor fixed duration treatment (FDT) — in combination with obinutuzumab (VenO), demonstrated cost savings at the US population level vs treat-to-progression (TTP) Bruton's tyrosine kinase inhibitor (BTKi) regimens (Li et al. ISPOR 2025). However, the impact of the Inflation Reduction Act (introducing Maximum Fair Price [MFP] for select drugs and a $2,000 Medicare Part D patient out-of-pocket [OOP] cap starting in 2025) on these costs remains unclear. This model estimated the annual total cost of care (TCC) for first-line FDT VenO vs TTP BTKi regimens among Medicare-eligible adults in the US, incorporating the MFP of the previously negotiated BTKi ibrutinib, as well as patient OOP costs after the implementation of the Part D cap. Methods: A US population model estimating the TCC for previously untreated CLL in adults (≥18 years) (Cho et al. PharmacoEconomics 2020; Fakhri et al. J Manag Care Spec Pharm 2025) was adapted for the Medicare-eligible subset (≥65 years) over 12 years (2019–2030).The model compared a hypothetical all FDT VenO-treated (assumed fixed duration of 1 year) vs an all TTP BTKi-treated population (ibrutinib ± rituximab/obinutuzumab, acalabrutinib ± obinutuzumab, or zanubrutinib). Patient cohorts entered the model annually and were followed for 5 years. CLL incidence rates were sourced from the Surveillance, Epidemiology, and End Results Program and applied to US Census data. Per-patient yearly costs by treatment were derived from a published TCC model (Cho et al. PharmacoEconomics 2020; Fakhri et al. J Manag Care Spec Pharm 2025), accounting for treatment, adverse event management, routine care, and monitoring costs. Drug costs used average wholesale acquisition costs from Truven Health Analytics Red Book® (2019–2024), with projections post-2024 based on historic trends unless MFP from Medicare negotiations were applied (e.g. ibrutinib price set at $9,319 effective January 1, 2026). The Medicare Part D OOP cap for 2025–2030 ($2,000 in 2025, with annual inflation-based adjustments) was applied to the patient cohort estimates to model the population-level OOP costs for the US Medicare-eligible population. Results: In 2019, the estimated payer cost for previously untreated CLL in Medicare-eligible adults was $1.41 billion (B) for a hypothetical all FDT VenO-treated population and $1.42B for an all TTP BTKi-treated population. By 2030, the estimated cost for an all FDT VenO-treated and all TTP BTKi-treated population was $3.57B vs $7.84B, respectively, accounting for the MFP for ibrutinib. Over 12 years, an all TTP BTKi-treated population would incur $40.5B more than an all FDT VenO-treated population, primarily due to continued drug costs. For the same previously untreated CLL Medicare-eligible modeled population, patient OOP costs in 2025 under the Part D cap were projected to be $12.1 million (M) for a hypothetical all FDT VenO-treated population vs $62.0M for a hypothetical all TTP BTKi-treated population. By 2030, patient OOP costs for an all FDT VenO-treated and all TTP BTKi-treated population were $15.9M vs $78.7M, respectively, primarily due to continued time on treatment for the all TTP BTKi cohort. Over 6 years post-Part D cap implementation (2025–2030), a hypothetical all FDT VenO-treated population could save Medicare-eligible patients with CLL $334M collectively in OOP costs compared with a hypothetical all TTP BTKi-treated population. Conclusions: Over 12 years (2019–2030), a hypothetical all FDT VenO-treated population could save Medicare up to $40.5B vs an all TTP BTKi-treated population when used as a first-line treatment for CLL, even with the implementation of MFP for a TTP BTKi. Although the Medicare Part D OOP cap limits the annual financial burden on Medicare-eligible patients, the fixed duration nature of VenO could further reduce costs, potentially saving patients up to $334M collectively from 2025–2030 when comparing a hypothetical all FDT VenO-treated population with a hypothetical all TTP BTKi-treated population with previously untreated CLL. Despite rising overall CLL costs and recent Inflation Reduction Act measures to manage costs, FDT regimens like VenO offer substantial cost savings for both payers and patients relative to TTP regimens.