Results from the phase 3 ASC4FIRST study presented at the 2024 American Society of Hematology Annual Meeting & Exposition showed that asciminib had a better benefit-risk profile compared with investigator-selected tyrosine kinase inhibitors (IS TKIs) in newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP).
The study compared the efficacy and safety/tolerability of asciminib to all four standard-of-care TKIs: imatinib, nilotinib, dasatinib, and bosutinib, which were selected by investigators before randomization.
Adults with newly diagnosed CML-CP were stratified by ELTS risk category and TKI, accounting for patient preference. Patients were randomized 1:1 to receive either asciminib 80 mg once daily or an IS TKI at label doses.
The efficacy results covered 201 patients randomized to asciminib and 204 to IS TKIs. The rates of optimal responses at week 12 (BCR::ABL1IS ≤10%) and week 24 (BCR::ABL1IS ≤1%), respectively, were higher with asciminib vs IS TKIs (89.6% vs 70.1%; 88.6% vs 63.7%). For imatinib, the respective figures were 88.1% vs 59.8% and 88.1% vs 52.9%. For the second-generation TKIs, the respective figures were 91.0% vs 80.4% and 89.0% vs 74.5%.
Safety analyses were done in patients who received asciminib (n=200), imatinib (n=99), and 2G TKIs (nilotinib, n=49; dasatinib, n=42; and bosutinib, n=11). Grade ≥3 AEs were lower with asciminib (38.0%) vs imatinib (44.4%), nilotinib (51.0%), dasatinib (54.8%), and bosutinib (72.7%). Any-grade AEs leading to treatment discontinuation were lower with asciminib (4.5%) vs imatinib (11.1%), nilotinib (8.2%), dasatinib (11.9%), and bosutinib (9.1%). Any-grade AEs leading to dose adjustment and/or interruption were lower with asciminib (30.0%) vs imatinib (39.4%), nilotinib (49.0%), dasatinib (54.8%), and bosutinib (63.6%).
“[Asciminib’s] superior efficacy vs all IS TKIs and more favorable safety/tolerability compared with each IS TKI [imatinib, nilotinib, dasatinib, and bosutinib] suggests that [asciminib] may transform the CML treatment paradigm,” the authors concluded.
Reference
Cortes J, Hochhaus A, Hughes T. Asciminib (ASC) demonstrates favorable safety and tolerability compared with each investigator-selected tyrosine kinase inhibitor (IS TKI) in newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) in the pivotal phase 3 ASC4FIRST study. Abstract #475. December 7-10; San Diego, California.
