Updated Results from the ASCEMBL Trial

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Dr. Aditi Sharma & Dr. Abhishek Mangaonkar - about phase III ASCEMBL Trial

By Dr. Aditi Sharma of Barbara Ann Karmanos Cancer Institute

& Dr. Abhishek Mangaonkar of Mayo Clinic


In the longer-term follow-up of the phase III ASCEMBL trial published in Leukemia, Andreas Hochhaus, MD and colleagues reported consistently superior efficacy of asciminib compared to bosutinib in patients with chronic myeloid leukemia in chronic phase (CML-CP) treated with ≥2 prior tyrosine kinase inhibitors (TKIs)1.


Patients with CML-CP who have failed two or more prior TKIs face limited therapeutic options due to emerging mutations, existing comorbidities, or treatment-related toxicities. Asciminib, the first BCR::ABL1 inhibitor to specifically target the ABL Myristoyl Pocket (STAMP), has shown superior efficacy and better safety than bosutinib, with almost doubled major molecular response (MMR) rate at 24 weeks in the primary analysis of the ASCEMBL study2. After 48 weeks of follow-up, asciminib continued to show increasing efficacy benefits compared with bosutinib, with no new or worsening safety findings compared to the primary analysis3. Asciminib was approved by the U.S. Food and Drug Administration in 2021 for treating adults with Philadelphia chromosome–positive CML-CP previously treated with ≥2 TKIs and for those with the BCR::ABL1 T315I mutation.


After a median follow-up of 2.3 years, authors report the longer-term efficacy and safety results in ASCEMBL which included patients 18 years or older with CML-CP treated with at least two prior ATP-competitive TKIs and who experienced treatment failure or were intolerant to their most recent TKI and excluded patients harboring T315I or V299L BCR-ABL1 mutations. Participants were randomly assigned in a 2:1 ratio to receive either asciminib 40 mg twice daily (N=157) or bosutinib 500 mg once daily (N=76). Stratification was based on major cytogenetic response status at baseline. The key secondary endpoint was the rate of MMR (BCR::ABL1IS ≤ 0.1%) at week 96 without having met any criteria for treatment failure (defined as lack of efficacy per 2013 European LeukemiaNet recommendations or treatment discontinuation for any reason) before this time point.


In this longer follow-up, authors report efficacy and safety analyses for data collected up to the cutoff date of October 6, 2021, when all randomized patients had completed their week 96 visit or discontinued earlier. Around 46% of patients in the asciminib arm and 80% in the bosutinib arm discontinued treatment with lack of efficacy (asciminib, 24.2%; bosutinib, 35.5%) being the most common reason for treatment discontinuation, followed by adverse events (AEs) (asciminib, 7%; bosutinib, 25%) and physician decision (asciminib, 9%; bosutinib, 8%).


After 96 weeks, the rate of MMR was higher with asciminib (37.6%) compared to bosutinib (15.8%), with a rate difference of 21.74% (95% CI, 10.53–32.95; p = 0.001) after adjusting for baseline major cytogenetic response (MCyR) status. Patients on asciminib achieved MMR earlier than those on bosutinib, and the probability of attaining MMR by week 96 was 41.2% with asciminib and 22.6% with bosutinib. The 2-year overall survival and progression-free survival rates for asciminib and bosutinib were in the high 90s with overlapping confidence intervals.


Asciminib had a lower incidence of all-grade (91% vs. 97%) and grade ≥3 (56% vs. 68%) AEs compared to bosutinib, despite being administered for a longer duration. The most common grade ≥3 AEs with asciminib were thrombocytopenia (22.4%) and neutropenia (18.6%), while with bosutinib, they were neutropenia (14.5%), diarrhea (10.5%), and increased alanine aminotransferase (ALT) (14.5%). AEs leading to treatment discontinuation were less frequent with asciminib (7.7% vs. 26.3%), and dose adjustments were also lower with asciminib (42.3% vs. 64.5%). However, asciminib had a higher incidence of arterial-occlusive events (5.1%) than bosutinib (1.3%).


To summarize, the updated results from ASCEMBL support higher rates of MMR with asciminib compared to bosutinib with no differences in 2-year overall or progression-free survival. For patients who are candidates for an allogeneic stem cell transplant, ascminib is a better alternative to bosutinib due to the higher and faster response rates.



1Hochhaus 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. 2023;37(3):617-626. doi:10.1038/s41375-023-01829-9

2Réa D, Mauro MJ, Boquimpani C, et al. A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior TKIs. Blood. 2021;138(21):2031-2041. doi:10.1182/blood.2020009984

3Mauro M, Minami Y, Rea D, Hochhaus A, Lomaia E, Voloshin S, et al. Efficacy and safety results from Ascembl, a multicenter, open-label, phase 3 study of asciminib, a first-in-classSTAMP inhibitor, vs bosutinib in patients with chronic myeloid leukemia in chronic phase after ≥2 prior tyrosine kinase inhibitors: update after 48 weeks. In: 63rd ASH Annual Meeting & Exposition. Atlanta, GA; 2021. Abstract 310.

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