Asciminib vs bosutinib in chronic-phase chronic myeloid leukemia previously treated with at least two tyrosine kinase inhibitors: longer-term follow-up of ASCEMBL
Andreas Hochhaus, Delphine Réa, Carla Boquimpani, Yosuke Minami, Jörge E. Cortes, Timothy P. Hughes, Jane F. Apperley, Elza Lomaia, Sergey Voloshin, Anna Turkina, Dong‐Wook Kim, André Abdo, Laura Fogliatto, Philipp le Coutre, Koji Sasaki, Dennis Dong Hwan Kim, Susanne Saußele, Mario Annunziata, Naeem Chaudhri, Lynette Chee, Valentín García‐Gutiérrez, S. S. Kapoor, Alex Allepuz, Sara Quenet, Véronique Bédoucha, Michael J. Mauro
Abstract
Asciminib, the first BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket (STAMP), is approved worldwide for the treatment of adults with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (CML-CP) treated with ≥2 prior tyrosine kinase inhibitors (TKIs). In ASCEMBL, patients with CML-CP treated with ≥2 prior TKIs were randomized (stratified by baseline major cytogenetic response [MCyR]) 2:1 to asciminib 40 mg twice daily or bosutinib 500 mg once daily. Consistent with previously published primary analysis results, after a median follow-up of 2.3 years, asciminib continued to demonstrate superior efficacy and better safety and tolerability than bosutinib. The major molecular response (MMR) rate at week 96 (key secondary endpoint) was 37.6% with asciminib vs 15.8% with bosutinib; the MMR rate difference between the arms, after adjusting for baseline MCyR, was 21.7% (95% CI, 10.53-32.95; two-sided p = 0.001). Fewer grade ≥3 adverse events (AEs) (56.4% vs 68.4%) and AEs leading to treatment discontinuation (7.7% vs 26.3%) occurred with asciminib than with bosutinib. A higher proportion of patients on asciminib than bosutinib remained on treatment and continued to derive benefit over time, supporting asciminib as a standard of care for patients with CML-CP previously treated with ≥2 TKIs.