Asciminib Demonstrated Superior Efficacy and Safety Compared to Bosutinib Among Patients With Philadelphia Chromosome-Positive Chronic Myeloid Leukemia

Results from the ASCEMBL Trial

Asciminib, a BCR::ABL1 inhibitor, demonstrated superior efficacy and safety compared to bosutinib among patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML-CP), according to findings from the ASCEMBL trial recently published in Leukemia.

Andreas Hochhaus, MD, Universitätsklinikum Jena, Jena, Germany, and coauthors stated, “For patients with CML-CP who are intolerant of or resistant to ≥2 prior [Tyrosine kinase inhibitors] (TKIs), therapeutic options become limited due to newly emerging mutations, existing comorbidities, or toxicities associated with previous treatments.” 

Prior research on asciminib, which specifically targets the ABL myristoyl pocket (STAMP), found that this drug may be highly efficacious in the treatment of CML-CP. To further investigate, the study authors compared the treatment efficacy and safety of asciminib versus bosutinib, a TKI commonly used to treat CML-CP. 

233 patients with CML-CP who had been treated with ≥2 prior TKIs and had experienced treatment failure were enrolled in this trial. Patients were randomly assigned to receive either asciminib (n = 157) at 40 mg twice daily or bosutinib (n = 76) at 500 mg once daily. 

At a median follow-up of 2.3 years, treatment was ongoing in 53.5% of patients (n = 84) receiving asciminib, and 19.7% (n = 15) receiving bosutinib, respectively. The median duration of exposure by the data cutoff was 23.7 months in the asciminib arm and 7 months in the bosutinib arm. The major molecular response rate at 96 weeks, a key secondary endpoint, was 37.6% in the asciminib arm versus 15.8% in the bosutinib arm. After an adjustment for baseline major cytogenetic response, the difference in major molecular response rates between the treatments was 21.7%. The 2-year estimated progression-free survival rate and overall survival rate were 94.4% and 97.3%, respectively, in the asciminib arm, and 91.1% and 98.6% in the bosutinib arm. 

The incidence of grade ≥ 3 adverse events was 56.4% in the asciminib arm versus 68.4% in the bosutinib arm. Asciminib demonstrated a significant reduction in adverse events leading to treatment continuation, with 7.7% of the asciminib arm discontinuing treatment compared to 26.3% of the bosutinib arm. The most common grade  ≥ 3 adverse events in the asciminib arm included thrombocytopenia (3.2%) and neutropenia (2.6%). The most common grade  ≥ 3 adverse events in the bosutinib arm included increased [alanine aminotransferase] (ALT) (3.9%), neutropenia (3.9%), and pleural effusion (2.6%). 

Dr Hochhaud et al concluded, “Results from ASCEMBL are a confirmation of the enduring clinical benefit of asciminib after longer exposure and continue to illustrate that asciminib has transformed CML treatment as a new standard of care for patients with CML-CP treated with ≥2 prior TKIs and support its ongoing development in earlier lines of therapy.”

Source: 

Hochhaus A, Réa D, Boquimpani C, et al. Asciminib vs bosutinib in chronic-phase chronic myeloid leukemia previously treated with at least two tyrosine kinase inhibitors: longer-term follow-up of ASCEMBL. Leukemia. Published online January 30, 2023:1-10. doi:10.1038/s41375-023-01829-9