Asciminib Demonstrates Superior Efficacy and Safety in Newly Diagnosed Chronic Myeloid Leukemia in the ASC4FIRST Trial Open Access

• Asciminib showed increasingly superior efficacy and favorable safety/tolerability vs all IS-TKIs, consistent with the primary analysis

• The week 96 analysis of ASC4FIRST confirms asciminib as a valuable frontline option for CML-CP

Many patients receiving frontline tyrosine kinase inhibitors (TKIs) for chronic phase chronic myeloid leukemia (CML-CP) experience inadequate disease control and/or adverse events (AEs) that impair quality of life. Treatments offering optimal efficacy, safety, and tolerability will support long-term therapy. In the primary analysis from ASC4FIRST, a phase 3 randomized trial comparing asciminib with investigator-selected TKIs (IS-TKIs) in newly diagnosed CML-CP, asciminib demonstrated superior efficacy vs all IS-TKIs and vs imatinib in the imatinib stratum, meeting both primary objectives. In the secondary analysis (2.2 years median follow-up), major molecular response (MMR) rate at week 96 was 74.1% with asciminib vs 52.0% with IS-TKIs (treatment difference, 22.4%; 95% CI, 13.6%-31.3%; 1-sided P<.001), and 76.2% with asciminib vs 47.1% with imatinib in the imatinib stratum (treatment difference, 29.7%; 95% CI, 17.6%-41.8%; 1-sided P<.001), meeting both key secondary objectives. MMR rate was 72.0% with asciminib vs 56.9% with second-generation (2G) TKIs (treatment difference, 15.1%; 95% CI, 2.3%-28.0%; 1-sided P<.05), suggesting possible clinical benefit although the study was not designed to formally confirm statistical significance for this secondary endpoint. Safety/tolerability remained favorable with asciminib vs IS-TKIs. Dose reductions and interruptions, respectively, occurred with asciminib (18.5% and 46.5%), imatinib (23.2% and 47.5%), and 2G TKIs (54.9% and 63.7%). The hazard ratio for time to discontinuation of treatment due to AEs for asciminib vs 2G TKIs was 0.46 (95% CI, 0.215%-0.997%). With longer follow-up, asciminib continued to demonstrate a favorable benefit-risk profile over IS-TKIs and imatinib, supporting its potential as a treatment option for newly diagnosed CML-CP.