Compared with bosutinib, asciminib appeared to improve clinical outcomes among some patients with chronic myeloid leukemia in chronic phase (CML-CP), according to research presented at the Annual Meeting of the Society of Hematologic Oncology (SOHO).
Asciminib is a novel BCR-ABL1-targeting tyrosine kinase inhibitor (TKI) that specifically targets the ABL myristoyl pocket. The phase 3 ASCEMBL was designed to evaluate the relative safety and efficacy of asciminib and bosutinib, a TKI commonly used in CML-CP.
A primary analysis of ASCEMBL data suggested that, among patients who had received at least 2 prior TKI therapy lines, asciminib improved the major molecular response (MMR) rate, with a lower toxicity rate. At SOHO 2022, the authors reported longer-term follow-up safety and efficacy data from ASCEMBL.
Overall, 233 patients were randomly assigned to receive asciminib (157 patients) or bosutinib (76 patients). Data cutoff was in October 2021; the median follow-up for this analysis was 2.3 years. At cutoff, 53.5% of patients in the asciminib group and 19.7% of patients in the bosutinib group were still receiving study treatment; 24.2% and 35.5% of patients, respectively, discontinued treatment because of lack of efficacy.
Analysis showed that the 96-week MMR rate was higher in the asciminib group (37.6%) than in the bosutinib group (15.8%); after adjustment for baseline major cytogenetic response, the difference was 21.7% (95% CI, 10.5%-33.0%). BCR::ABL1IS levels of 1% or less were, similarly, more common at week 96 among patients in the asciminib group.
The noted responses were durable with both TKIs. The median time to treatment failure was, however, longer with asciminib than with bosutinib (24 months vs 6 months, respectively).
Adverse events leading to treatment discontinuation occurred in 7.0% of patients treated with asciminib vs 25.0% of patients with bosutinib.
“MMR more than doubled with asciminib over bosutinib, and the difference in MMR rates increased between the 2 arms from 12.2% at week 24 to 21.7% at week 96,” the authors noted. “These results support the use of asciminib as a new CML therapy.”
Réa D, Hochhaus A, Mauro MJ, et al. Efficacy and safety results from ASCEMBL, a phase iii study of asciminib vs. bosutinib in patients with chronic myeloid leukemia in chronic phase (CML-CP) after ≥2 prior tyrosine kinase inhibitors (TKIs): week 96 update. Presented at: Annual Meeting of the Society of Hematologic Oncology (SOHO); September 28-October 1, 2022. Abstract CML-395.