Asciminib vs bosutinib in chronic-phase chronic myeloid leukemia previously treated with at least two tyrosine kinase inhibitors: longer-term follow-up of ASCEMBL

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.

Fig. 1. MMR and BCR::ABL1^IS ≤ 1% at week 96.

A The MMR graph shows the MMR rates at week 96 for asciminib and bosutinib. B The BCR::ABL1^IS ≤ 1% graph shows the BCR::ABL1^IS ≤ 1% rate at week 96 for asciminib and bosutinib. MCyR major cytogenetic response, MMR major molecular response (BCR::ABL1^IS ≤ 0.1% on the International Scale). *Based on the full analysis set. ^†The MMR rate difference between the two arms after adjusting for baseline MCyR status was 21.74% (95% CI, 10.53–32.95; two-sided p = 0.001). ^‡Based on 142 of 157 (90.4%) patients receiving asciminib and 72 of 76 (94.7%) receiving bosutinib with BCR::ABL1^IS > 1% at baseline. ^§The BCR::ABL1^IS ≤ 1% rate difference between the two arms after adjusting for baseline MCyR status was 26.02% (95% CI, 13.48–38.56; two-sided p = 0.000).

Fig. 2. MMR rate difference (95% CI) between treatment at week 96 from subgroup analyses.

A forest plot shows the MMR rate difference between treatment arms with 95% CIs at week 96 from subgroup analyses. MMR, major molecular response (BCR::ABL1^IS ≤ 0.1% on the International Scale); TKI tyrosine kinase inhibitor. *Patients with T315I and V299L BCR::ABL1 mutations or a non-evaluable mutation assessment were excluded from the subgroup analysis.

Fig. 3. Cumulative incidence of MMR and of BCR::ABL1^IS ≤ 1%.

A The cumulative incidence of MMR curve shows the probability of achieving MMR over time in each treatment arm. B The cumulative incidence of BCR::ABL1^IS ≤ 1% curve shows the probability of achieving BCR::ABL1^IS ≤ 1% over time in each treatment arm. Both were calculated using a competing risk analysis. MMR major molecular response (BCR::ABL1^IS ≤ 0.1% on the International Scale). *Non-responders were censored at their last molecular assessment date. ^†Discontinuation from treatment for any reason without prior achievement of MMR is considered a competing event. ^‡Based on 142 of 157 (90.4%) patients receiving asciminib and 72 of 76 (94.7%) receiving bosutinib with BCR::ABL1^IS > 1% at baseline. ^§Discontinuation from treatment for any reason without prior achievement of BCR::ABL1^IS ≤ 1% is considered a competing event.

Fig. 4. All-grade AEs by time period with asciminib.

A The first-ever adverse events (AEs) graph shows the incidence of AEs over time. B The first-ever, recurring, and ongoing AEs graph shows the prevalence of AEs over time. AE adverse event, ALT alanine aminotransferase, AST aspartate aminotransferase. *Includes thrombocytopenia and platelet count decreased. ^†Includes neutropenia and neutrophil count decreased. ^‡A patient with multiple occurrences of an AE is counted only once in that time period. Percentages were rounded to zero decimal places. The denominator for incidence is the number of patients ongoing at the beginning of each time period who have not yet experienced the event. The denominator for prevalence is the number of patients ongoing at the beginning of each time period.