The Impact of Asciminib on Patients With Pretreated CML-CP

Key Takeaways:

• The ASC4OPT clinical trial assessed the efficacy of asciminib among patients with chronic myeloid leukemia in chronic phase (CML-CP) with suboptimal responses to prior therapies.
• Within the main cohort, 39.4% of patients achieved major molecular response (MMR) by week 48, and this percentage increased to 43.6% at week 96.
• Asciminib was associated with high rates of adverse events (AEs) but lower symptom scores, resulting in a manageable safety profile similar to that of previous research.

The ASC4OPT clinical trial compared different dosing schedules of asciminib in order to optimize treatment for patients with CML-CP who had already been treated with, and stopped responding to, tyrosine kinase inhibitors (TKIs).

Study Methods and Outcomes

The primary outcome of the study was MMR rate at week 48. Secondary outcomes included MMR rate at week 96, time to MMR, complete cytogenetic response (CCyR), and safety.

The study’s main cohort included 169 patients not in MMR who were randomly assigned asciminib either 40 mg twice daily (85 patients) or 80 mg once daily (84 patients). Forty patients in this cohort (16 in the 40 mg group and 24 in the 80 mg group) had their asciminib doses raised to 200 mg once daily due to a lack of MMR at week 48.

The study also contained an exploratory cohort of 30 patients who were in MMR at baseline and were also randomly assigned to receive either 40 mg twice daily (14 patients) or 80 mg once daily (16 patients) of asciminib.

Comparing Doses of Asciminib Among Patients With CML-CP

At week 48, the average MMR rate in the main cohort was 39.4%, with rates of 43.4% in the 40 mg group and 35.4% in the 80 mg group. By week 96, the average MMR rate increased to 43.6%, with 45.8% in the 40 mg group and 41.5% in the 80 mg group.

Among the 40 patients who had their doses escalated to 200 mg, 17.5% achieved MMR by week 96.

In the exploratory cohort, most patients remained in MMR during the course of the study, 93.3% at week 48 and 86.7% at week 96.

Among patients who achieved MMR, the median time to MMR was 22.7 weeks, with 13.1 weeks in the 40 mg group and 23.9 weeks in the 80 mg group.

At week 48, the average CCyR rate was 58.2%, with rates of 60.2% in the 40 mg group and 56.1% in the 80 mg group.

Safety and Tolerability of Asciminib

Patient-reported symptom scores decreased after week 4, indicating slight improvement in quality of life for patients with CML-CP.

In the main cohort, 94% of patients experienced an adverse event (AE), with 37.5% experiencing an AE of grade 3 or higher. In the exploratory cohort, 96.7% of patients experienced an AE, with 46.7% experiencing a severe AE.

Implications for Managed Care

The ASC4OPT study highlighted the efficacy of asciminib in treating patients with pretreated CML. The dosing regimens demonstrated comparable effectiveness, with 40 mg twice daily having slightly better outcomes than 80 mg once daily.

The authors said, “Long-term results from ASC4OPT will provide further insights into the optimization of asciminib treatment.”

Overall, these findings indicate asciminib as potential standard-of-care for patients with CML who are not responding to TKI therapy.

Reference

Hochhaus A, le Coutre P, Milojkovic D, et al. ASC4OPT: asciminib treatment optimization study in patients with chronic myeloid leukemia in chronic phase previously treated with two or more tyrosine kinase inhibitors. Leukemia. 2026;40:1296-1305. doi:10.1038/s41375-026-02965-8