Objective: To evaluate the budget impact of a fixed-duration combination (FC) “acalabrutinib + venetoclax” regimen for treatmentnaive adults with chronic lymphocytic leukemia (CLL), unmutated IGHV, and absence of del(17p) or mutations in TP53 in the Russian Federation.Material and methods. A deterministic, payer-perspective model was developed over one- and three-year horizons. The analysis focused on drug acquisition costs (national price registry, +10% value added tax), with label-based dosing. The standard therapy included Bruton’s tyrosine kinase inhibitors (acalabrutinib, ibrutinib, or zanubrutinib), or FCs “venetoclax + obinutuzumab” and “ibrutinib + venetoclax”. The simulated scenario assumed a 50% substitution of “ibrutinib + venetoclax” by “acalabrutinib + venetoclax” over three years. A one way sensitivity analysis was performed to evaluate the impact of variations in drug prices (±20%), population size (±20%), and uptake of “acalabrutinib + venetoclax” (–20% to complete substitution).Results. The target population included 697 patients. Per-patient costs of FCs were as follows: 9,124,560 rubles for “acalabrutinib + venetoclax”; 10,375,643 rubles for “ibrutinib + venetoclax”. For the total cohort, total three-year expenditures amounted to 8,404.5 million rubles in the current practice versus 8,322.0 million rubles with FC “acalabrutinib + venetoclax”, i.e., budget savings came to 82.5 million rubles. These savings are driven by the lower cost for a course of “acalabrutinib + venetoclax” compared to “ibrutinib + venetoclax”. Sensitivity analyses confirmed robustness: although results were most sensitive to the prices of acalabrutinib and ibrutinib, savings persisted across tested ranges; higher uptake of “acalabrutinib + venetoclax” further increased budget savings.Conclusions. Implementing the FC “acalabrutinib + venetoclax” for the first-line treatment of CLL patients with unmutated IGHV and no TP53 aberrations reduces the healthcare budget burden compared to “ibrutinib + venetoclax”, yielding approximately 82.5 million rubles in savings over three years based on drug acquisition costs.