Asciminib in patients with newly diagnosed chronic myeloid leukemia: results from the Japanese subgroup of ASC4FIRST

Introduction: The phase III ASC4FIRST study (NCT04971226) demonstrated superior efficacy and favorable safety and tolerability for asciminib against investigator-selected tyrosine kinase inhibitors (IS-TKI) in newly diagnosed chronic myeloid leukemia (CML). Results of a subgroup analysis in Japanese patients are presented here. Methods: Adult patients were randomized 1:1 to asciminib or IS-TKI following stratification by European Treatment and Outcome Study long-term survival risk score and prerandomization-selected TKI (imatinib and second-generation [2G] TKI strata). At week 48, major molecular response (MMR) rate in all patients and imatinib stratum (primary endpoints) were assessed along with MR4.0, MR4.5, and safety (cutoff: November 28, 2023). Results: In Japanese patients (asciminib, n = 21; IS-TKI, n = 17 [imatinib/2G TKI, n = 8/9]), the MMR rate was higher with asciminib (81.0%) than IS-TKI (47.1%), and versus imatinib (asciminib: 100%; imatinib: 25.0% [imatinib stratum]). More patients on asciminib than IS-TKI achieved MR4.0 (57.1% vs. 11.8%) and MR4.5 (28.6% vs. 5.9%). Fewer grade ≥ 3 adverse events (AEs; 42.9%, 50.0%, and 55.6%) and AEs leading to treatment discontinuation (0%, 37.5%, and 11.1%) occurred with asciminib than imatinib or 2G TKI. Conclusion: Outcomes in Japanese patients were consistent with the ASC4FIRST overall population. Asciminib may be a therapy of choice for Japanese patients with CML.