Treatment cost per AE symptom-free day of asciminib and second-generation tyrosine kinase inhibitors in newly diagnosed patients with chronic myeloid leukemia

Abstract Background: While the overall survival for patients with chronic myeloid leukemia (CML) has improved significantly after the introduction of tyrosine kinase inhibitors (TKI), tolerability of these treatments—including second generation (2G) tyrosine kinase inhibitors—remains a challenge for some patients, who experience a variety of adverse events. Asciminib is a BCR::ABL1 inhibitor that has demonstrated greater major molecular response and more favorable tolerability in newly diagnosed CML-Chronic Phase (CP) patients compared to 2G TKIs in a multicenter, phase III randomized controlled trial (ASC4FIRST, NCT04971226). Due to the high cost of TKI treatments, it is essential to not only measure clinical outcomes but also quantify the health economic value of any differences in outcomes. This study aims to bridge this knowledge gap by estimating the differences in outcome value between asciminib and 2G TKIs (bosutinib, dasatinib, and nilotinib) using a novel cost per adverse event (AE) symptom-free day metric. Methods: The study evaluated cost per AE symptom-free day for adult, newly diagnosed patients with CML-CP receiving asciminib or 2G TKIs (dasatinib, nilotinib, bosutinib). A day was defined as “AE symptom-free” if the patient was (i) on therapy and (ii) had no symptomatic adverse events (AEs), defined as a non-hematologic and non-laboratory AE. Cost per AE symptom-free day was calculated as the cost of treatment over a 96-week treatment period divided by the number of AE symptom-free days over the first 96 weeks of treatment. Median and mean number of AE symptom-free days for asciminib and aggregated 2G TKIs were estimated from ASC4FIRST. Treatment cost over 96 weeks was calculated by summing drug acquisition costs with AE management costs. Drug acquisition costs were calculated using US 2025 wholesale acquisition costs (WAC) and FDA label-based dosing. AE management costs were calculated as the average of medical and pharmacy costs for treating symptomatic AEs weighted by the observed frequency of the AEs among asciminib-treated and 2G TKI-treated patients in ASC4FIRST (Cortes et al. Blood 2024;144[1]: 475; Hochhaus et al. N Eng J Med 2024; 391[10]: 885). The 2G TKI costs were calculated as a weighted average of individual 2G TKI costs based on their relative prescribing frequency observed in the ASC4FIRST trial. Because generic dasatinib and nilotinib became available in 2024 and 2025, their cost was calculated as a weighted average of generic and branded WAC, with US market share of imatinib from one year after imatinib genericization as a proxy (branded: 42%, generic: 58%). Results: At 96 weeks, the median treatment duration was 673.0 days for both asciminib and 2G TKI cohorts. Asciminib-treated patients experienced a median of 172.0 AE symptom-free days vs. 67.0 days for 2G TKI-treated patients (Δ=105.0 days). Mean number of AE symptom-free days was 271.9 for asciminib-treated vs. 180.9 for 2G TKI-treated patients (Δ=91.0 days). Treatment cost over the 96-week treatment period was $528,798 for asciminib vs. $437,911 for 2G TKIs (Δ= $90,887). Cost per median AE symptom-free day was 53.0% lower with asciminib than 2G TKIs ($3,074 vs. $6,536, Δ=-$3,462). Cost per mean AE symptom-free day was also lower with asciminib than 2G TKIs ($1,945 vs. $2,421, Δ=-$476). Conclusions: Patients on asciminib experience more AE symptom-free days on treatment relative to 2G TKIs. Treatment cost per median and mean AE symptom-free day was lower for asciminib relative to 2G TKIs.