Comparing Asciminib With Bosutinib in Patients With Chronic-Phase Chronic Myeloid Leukemia

According to results from the ASCEMBL trial, asciminib was superior to bosutinib in inducing major molecular responses (MMR) in patients with chronic myeloid leukemia in chronic-phase (CML-CP) that was resistant or intolerant to two lines of tyrosine kinase inhibitor (TKI) treatment. The findings were reported at the 2021 American Society of Hematology Annual Meeting by Michael J. Mauro, MD, of Memorial Sloan Kettering Cancer Center in New York.

Asciminib is the first BCR-ABL1 inhibitor that potently inhibits kinase activity of the BCR-ABL1 oncoprotein by Specifically Targeting the ABL Myristoyl Pocket (STAMP), the investigators explained. In the primary analysis from ASCEMBL, a randomized, phase III trial, asciminib demonstrated superior efficacy and a better safety and tolerability profile than bosutinib, with 24-week MMR rates of 25.5% versus 13.2%. Grade ≥3 adverse events (AEs) were reported in 50.6% and 60.5% of patients receiving asciminib and bosutinib, respectively, and AEs leading to discontinuation in 5.8% and 21.1%, respectively. The present analysis updates these results, after a median follow-up of 19.2 months (or 7.5 months’ additional follow-up since the primary analysis).

A total of 233 eligible ASCEMBL participants were randomized 2:1 to receive asciminib 40 mg twice daily (n = 157) or bosutinib 500 mg once daily (n =76). At data cutoff, all randomized patients had completed a follow-up visit at week 48 or had discontinued earlier. Eighty-nine patients (56.7%) were still receiving asciminib, and 17 (22.4%) were still receiving bosutinib. The most common reason for treatment discontinuation was lack of efficacy, which occurred in 37 asciminib-treated patients (23.6%) and 27 bosutinib-treated patients (35.5%).

By week 48, the cumulative incidence of MMR was 33.2% with asciminib and 18.6% with bosutinib, demonstrating that the difference observed at week 24 was maintained through longer follow-up. The authors noted that, at baseline, 50.8% of asciminib-treated patients who did not achieve an MMR had BCR-ABL1IS ≤1% by week 48 (compared with 33.7% of bosutinib-treated patients).

The difference in deep molecular responses (MR) favoring asciminib over bosutinib persisted by week 48:

  • MR4(BCR-ABL1IS ≤0.01%): 14.0% with asciminib and 6.6% with bosutinib
  • MR5(BCR-ABL1IS ≤0.0032%): 9.6% with asciminib and 2.6% with bosutinib

“With a longer duration of exposure in the asciminib arm, the safety and tolerability profile in the current analysis remains similar to that at the primary analysis,” the authors reported. After a median duration of exposure of 67.1 weeks for asciminib and 29.7 weeks for bosutinib, 91.0% and 97.4% of patients, respectively, reported at least one adverse event (AE). Approximately 54.5% of asciminib-treated patients and 67.1% of bosutinib-treated patients reported experiencing at least one grade ≥3 AE. No additional fatal events were reported since the primary analysis, the researchers noted.

Asciminib was associated with fewer AEs leading to discontinuation (7.1% vs. 25.0%). The most common AEs leading to treatment discontinuation included thrombocytopenia (3.2%) and neutropenia (2.6%) in the asciminib arm and increased alanine aminotransferase (5.3%) and neutropenia (3.9%) in the bosutinib arm. “Myelosuppression, while more prominent [with asciminib], appears to be early and disease-related,” the authors added.

The authors concluded that, “resistant/intolerant CML-CP after two lines of TKI treatment remains BCR-ABL1 dependent.” According to these findings, “the novel STAMP inhibitor asciminib demonstrates continued superior efficacy and a limited adverse event profile,” with a positive benefit-risk profile that continues to support the use of asciminib as a new therapy in this heavily pretreated patient population.