Asciminib in late-line CML treatment

In this issue of Blood Advances, Mauro et al 1 report the 4-year results of the ASCEMBL trial, which compared asciminib vs bosutinib for patients with chronic myeloid leukemia in chronic phase (CP-CML) after ≥2 previous tyrosine kinase inhibitors (TKIs).The primary end point of ASCEMBL was the rate of major molecular response (MMR) at 24 weeks, and a key secondary end point was the rate of MMR at 96 weeks.This study met these end points, with more asciminib-treated patients achieving this response at both time points (25.5% vs 13.2%, and 37.6% vs 15.8%, respectively).2,3 The earlier results from this study also report fewer grade ≥3 adverse events (AEs) and AEs leading to treatment discontinuation with asciminib compared with bosutinib.2,3 This article reports the end of study (EOS) analysis after a median of 3.7 years on treatment and 5 years from the time the last patient was enrolled.Crossover was allowed for bosutinib-treated patients who met the European Leukemia Network 2013 definition of treatment failure at ≤96 weeks after the last patient was randomized.This study enrolled 233 patients with a 2:1 randomization to asciminib vs bosutinib.At the EOS, 36.5% completed protocol-driven treatment.The most common reasons for treatment discontinuation were lack of efficacy (25.5% with asciminib, 36.8% with bosutinib) and AEs (7% with asciminib, 27.6% with bosutinib).The increased MMR rate with asciminib vs bosutinib was maintained at the 156-week analysis (33.8% vs 10.5%, respectively).When looking specifically at patients with baseline International Standardization (IS) of BCR::ABL1 IS of >1%, 43% of asciminib-treated patients and 11.1% of bosutinib-treated patients had achieved BCR::ABL1 IS of ≤1% at 156 weeks.The durability of these responses was similar with both drugs.Importantly, no significant difference in progressionfree survival or overall survival was seen between the 2 groups, although this included 25 patients who switched from bosutinib to asciminib.Notably, of the patients who discontinued asciminib owing to lack of efficacy, 38.1% had acquired new BCR::ABL1 mutations.