With a median follow-up of more than 2 years, researchers from the ASCEMBL study reported that asciminib continues to have superior efficacy and better safety compared with bosutinib among patients with chronic myeloid leukemia in chronic phase (CML-CP). These findings were presented by Jorge E. Cortes, MD, of the Georgia Cancer Center, Augusta, Georgia, at the 2022 ASCO Annual Meeting.
At week 96, the major molecular response (MMR) rate was 37.6% for asciminib compared with 15.8% for bosutinib. After adjusting for baseline major cytogenetic response status, the difference was 21.7% (2-sided P =.001).
Asciminib is the first BCR::ABL1 inhibitor to specifically target the ABL myristoyl pocket (STAMP). It is currently approved by the U.S. Food and Drug Administration for the treatment of adults with Philadelphia chromosome-positive (Ph+) CML-CP who previously received 2 or more tyrosine kinase inhibitors (TKIs) and in those with the T315I mutation.
The phase 3 study (ClinicalTrials.gov Identifier: NCT03106779) included 233 patients with CML-CP after 2 or more prior TKIs who had intolerance or lack of efficacy on their last TKI per 2013 European LeukemiaNet criteria. The patients were randomly assigned 2:1 to asciminib 40 mg twice daily or bosutinib 500 mg once daily.
The primary analysis at week 24 showed superior efficacy on MMR rate with asciminib compared with bosutinib in this patient population (adjusted difference, 12.2%). The MMR rate remained higher with asciminib at a week 48 analysis as well (adjusted difference, 16.1%).
With a median follow-up of 2.3 years, 53.5% of patients assigned to asciminib and 19.7% of patients assigned to bosutinib were still on treatment. The most common reason for discontinuation was lack of efficacy.
The improvement in MMR rate seen at week 96 with asciminib vs bosutinib was consistent across all demographic and prognostic subgroups, the researchers noted. The probability of maintaining MMR for at least 72 weeks was 96.7% for asciminib and 92.9% for bosutinib.
Additionally, a larger share of patients on asciminib had a BCR:ABL1 International Scale transcript level of 1% or less as compared with bosutinib (45.1% vs 19.4%).
Median duration of exposure was 23.7 months for asciminib and 7.0 months for bosutinib. The researchers noted that despite the longer duration of exposure to asciminib, safety and tolerability remained better than that with bosutinib.
The most frequent grade 3 and higher adverse events on asciminib vs bosutinib were thrombocytopenia (22.4% vs 9.2%), neutropenia (19.9% vs 15.8%), diarrhea (0% vs 10.5%), and increased alanine aminotransferase level (0.6% vs 14.5%).
On the basis of these results, the researchers suggest that asciminib has “the potential to transform standard of care” for these patients.
Disclosure: This research was supported by Novartis. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Rea D, Mauro MJ, Hochhaus A, et al. Efficacy and safety results from ASCEMBL, a phase 3 study of asciminib versus bosutinib (BOS) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) after ≥2 prior tyrosine kinase inhibitors (TKIs): Week 96 update. Presented at ASCO 2022; June 3-7, 2022. Abstract 7004.