Dr Cortes on Asciminib’s Superior Efficacy and Safety in First-Line CML

“Nearly all the adverse [effects] are less common with asciminib compared [with] other second-generation TKIs, so [we’re seeing] a very good risk-benefit ratio in favor of asciminib in this longer follow-up.”

Jorge Cortes, MD, director, Georgia Cancer Center, Augusta University, discuses 96-week follow-up findings from the phase 3 ASC4FIRST study (NCT04971226) evaluating asciminib (Scemblix) as a first-line treatment for patients with chronic myeloid leukemia in chronic phase (CP-CML) compared with investigator-selected TKIs, including imatinib (Gleevec) and second-generation TKIs.

The FDA approval of asciminib on October 29, 2024, for the treatment of adult patients with newly diagnosed, Philadelphia chromosome–positive CP-CML was based on the 48-week major molecular response (MMR) data from the ASC4FIRST trial.

The subsequent 96-week follow-up analysis highlighted sustained and improved molecular response rates with asciminib over time, with significant advantages observed in both primary and exploratory comparisons, Cortes adds. Notably, even though the study was not powered for comparisons with second-generation TKIs, asciminib seemed to demonstrate better efficacy in this subgroup, further reinforcing its potential as a frontline therapy, he reports.

Data presented at the 2024 ASH Annual Meeting showed that the MMR rate at week 96 remained superior among patients who received asciminib (n = 201) vs those receiving investigator-selected TKIs (n = 204). The 96-week MMR rates were 74.1% and 52.0%, respectively, with a difference of 22.4% (95% CI, 13.6%-31.3%; P < .001). This represented an increase in MMR as the 48-week MMR rates were 67.7% and 49.0%, respectively, which originally met the primary end point of the trial.

Safety data showed that asciminib was well tolerated, with treatment discontinuation due to adverse effects (AEs) reported in only 5% of patients compared with 12.9% for imatinib and second-generation TKIs, Cortes notes. Additionally, asciminib was associated with fewer grade 3 or 4 AEs, fewer dose reductions, and fewer treatment interruptions than other TKIs. Importantly, the median average daily dose of asciminib was 80 mg/day, reflecting its favorable tolerability, he emphasizes.

The safety analysis also demonstrated that asciminib had a comparable or lower incidence of overall and grade 3/4 AEs compared with imatinib, Cortes states. These differences were even more pronounced when comparing asciminib with second-generation TKIs, where nearly all AEs occurred less frequently with asciminib, further highlighting its favorable risk-benefit profile, he adds.