Asciminib remained superior vs bosutinib in late-line CML-CP after nearly 4 years of follow-up in ASCEMBL.

Abstract

The efficacy of and disease control afforded by tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia in chronic phase (CML-CP) has led to increased longevity and thus continued pursuit of alternative therapies that are efficacious and maximize tolerability. The 24- and 96-week analyses from ASCEMBL demonstrated superior efficacy, safety, and tolerability of asciminib compared with bosutinib in later-line therapy, meeting primary and key secondary objectives, respectively. With nearly 4 years of follow-up, data from ASCEMBL continued to demonstrate superior efficacy, better safety, and greater tolerability of asciminib compared with bosutinib. At week 156, the major molecular response (MMR) rates remained higher with asciminib (33.8%) than bosutinib (10.5%); the difference in MMR rates between arms, after adjusting for baseline major cytogenetic response, was 23.2% (95% CI, 13.14%-33.18%; 2-sided P<0.001). Asciminib continued to cause fewer grade ≥3 adverse events (AEs) (59.6% vs 68.4%) and AEs leading to treatment discontinuation (8.3% vs 27.6%) than bosutinib. This updated analysis also includes patients who switched to asciminib due to lack of efficacy with bosutinib. Two of 25 patients who switched achieved MMR by the end of study, suggesting that earlier incorporation of asciminib, before other TKIs, may improve responses, albeit modestly. These long-term results further solidify asciminib as the therapy of choice for patients with CML-CP previously treated with ≥2 prior TKIs. This trial was registered at ClinicalTrials.gov as NCT03106779.