Asciminib Provides Better Efficacy and Favorable Safety and Tolerability Against Investigator-Selected Tyrosine Kinase Inhibitors in East Asian Patients With Newly Diagnosed Chronic Myeloid Leukemia: Results From a Subgroup Analysis of the Pivotal ASC4FIRST Study.

Abstract / Summary

ASC4FIRST (ClinicalTrials.gov NCT04971226) is a pivotal phase 3 clinical trial comparing the efficacy and safety of asciminib vs. standard of care (SoC) tyrosine kinase inhibitors (TKIs) in newly diagnosed patients with chronic myeloid leukemia in chronic phase (CML-CP). The study demonstrated superior efficacy and a favorable safety profile for asciminib vs. all current SoC TKIs; this subgroup analysis involved 138 patients from East Asian sites enrolled in ASC4FIRST. Patients were randomized to receive either asciminib or investigator-selected TKIs (IS-TKIs: imatinib, bosutinib, dasatinib, or nilotinib) following stratification by risk category and prerandomization-selected TKI (imatinib or second-generation TKI). Consistent with non-East Asian patients, asciminib showed better efficacy in East Asian patients, with a major molecular response (MMR) rate at Week 48 and Week 96 of 64.9% and 77.0% compared to 45.3% and 57.8% for all IS-TKIs combined, respectively (common treatment difference: 19.5% and 20.0%, respectively). Similar results were obtained for patients with imatinib as the prerandomization-selected TKI (MMR rate at Week 48 and Week 96: 67.9% and 78.6% for asciminib compared to 30.8% and 46.2% for imatinib, respectively; common treatment difference: 36.5% and 32.7%, respectively). Asciminib also showed a favorable safety profile in East Asian patients, with lower rates of Grade ≥ 3 adverse events (AEs) and AEs leading to discontinuation compared to IS-TKIs (41.9% vs. 54.0% and 2.7% vs. 9.5%, respectively), consistent with the results from non-East Asian patients. These findings support the use of asciminib as a first-line treatment option for East Asian and non-East Asian patients with CML-CP.

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