Work

Venetoclax in combination with ponatinib for the treatment of asciminib-resistant chronic myeloid leukemia

Year: 2025

Type: article

Abstract: Asciminib, an allosteric inhibitor specifically targeting the myristoyl pocket of BCR::ABL1, has expanded therapeutic options for heavily pretreated patients with chronic myeloid leukemia (CML), and for those with the BCR::ABL1 T315I mutation [ 1 , 2 , 3 ]. Several clinical studies evaluating asciminib in frontline CML therapy are currently ongoing (e.g., ASCI4FIRST, ASCI4START, ASCEND), with promising preliminary results indicating superior efficacy, improved tolerability, and a lower rate of treatment discontinuation due to toxicity compared to ATP-competitive inhibitors [ 4 , 5 , 6 ]. However, clinical trials of asciminib in both advanced-line and first-line CML treatment also report the emergence of resistance, often due to acquired or persisting mutations in BCR::ABL1 [ 2 , 4 ]. The full spectrum of these mutations remains unidentified, underscoring the need for further investigation and the exploration of backup therapeutic strategies, including combination therapies.

Source: Leukemia

DOI: 10.1038/s41375-025-02732-1