Multinational phase 3 trial of asciminib for newly diagnosed chronic myeloid leukemia

Patients with newly diagnosed chronic myeloid leukemia (CML) need long-term therapy with high efficacy and safety. Asciminib is a BCR::ABL1 inhibitor specifically targeting the ABL myristoyl pocket. The multinational phase 3 ASC4FIRST trial randomized patients with newly diagnosed CML 1:1 to oral asciminib 80 mg once daily or an investigator-selected tyrosine kinase inhibitor (TKI). The median follow-up was 16.3 months in the asciminib group and 15.7 months in the comparator group. A major molecular response at week 48 occurred in 67.7% of patients in the asciminib group, as compared with 49.0% in the comparator group (p<0.001), and in 69.3% of patients in the asciminib group as compared with 40.2% in the imatinib group within the imatinib stratum (p<0.001), and in 66.0% of patients in the asciminib group as compared to 57.8% with second-generation TKIs in the second-generation TKI stratum. Adverse events of grade 3 or higher and events leading to discontinuation of the trial regimen were less frequent with asciminib (38.0% and 4.5%, respectively) than with imatinib (44.4% and 11.1%) and second-generation TKIs (54.9% and 9.8%). The authors conclude that among patients with newly diagnosed CML, asciminib showed superior efficacy and a favorable safety profile compared with imatinib and investigator-selected TKIs.