Asciminib Associated With Durable Molecular Responses Among Patients With CML-CP

Key Takeaways:

• Asciminib 200 mg twice daily (BID) was associated with durable responses among patients with T315I-mutated chronic myeloid leukemia in chronic phase (CML-CP).
• Ponatinib-naive patients achieved significantly higher rates of major molecular response (MMR) compared to ponatinib-pretreated patients.
• Incidences of adverse events (AEs) were comparable to those recorded in previous studies, with overall low severity and low rates of treatment discontinuation.

The T315I mutation is a BCR::ABL1 mutation among patients with CML-CP that is associated with treatment resistance and poor survival outcomes.

Asciminib is the first BCR::ABL1 inhibitor and was approved by the US Food and Drug Administration in 2021 to treat T315I-mutated CML-CP. The approval was based on data from a first-in-human phase 1 dose-finding trial that assessed the safety and efficacy of asciminib 200 mg BID.

Study Methods and Outcomes

A subsequent analysis of the phase 1 trial examines the final study results among 48 patients with T315I-mutated CML-CP at baseline who received asciminib 200 mg BID after 6 or less years of therapy.

Outcomes included AEs and molecular responses.

Asciminib Efficacy

BCR::ABL1 levels of 1% or lower were observed in 25 (55.6%) patients at week 24. The proportion of patients increased to 31 (68.9%) by week 300.

Twenty-four (53.3%) patients achieved MMR, with 20 patients achieving MMR by week 24. In addition, 20 patients maintained or deepened their response by the end of the study, and 4 lost MMR.

Rates of MMR were significantly higher among ponatinib-naive patients compared to ponatinib-pretreated patients, 73.7% vs 38.5%, respectively. This finding indicates the clinical benefit of prescribing asciminib before ponatinib among patients with T315I-mutated CML-CP.

Asciminib Tolerability

Treatment discontinuation occurred in 23 (47.9%) patients, mainly due to poor response and AEs. At the end of the study, 25 (52.1%) continued receiving asciminib via posttrial access.

Asciminib demonstrated a safety profile comparable to that of prior studies, with no new or worsening safety signals being observed.

Most patients experienced AEs during the first year of asciminib therapy, with the most common side effects being fatigue, increased lipase, diarrhea, and nausea. The most common severe AEs (grade 3 or higher) included increased lipase, thrombocytopenia, and neutropenia. AEs interrupted treatment for 21 patients.

Implications for Managed Care

These findings demonstrate the effectiveness and tolerability of asciminib 200 mg BID in treating patients with T315I-mutated CML-CP, even after prolonged exposure. The authors noted that even after up to 6 years of expose, half the study’s participants continue receiving asciminib.

Reference

Cortes JE, Rea D, Mauro M, et al. Asciminib monotherapy in patients with BCR::ABL1 T315I-mutated chronic-phase chronic myeloid leukemia: phase 1 trial final results. Leukemia. 2026;40:1893–1900. doi:10.1038/s41375-026-02972-9