Asciminib: an investigational agent for the treatment of chronic myeloid leukemia

Introduction: Tyrosine kinase inhibitors (TKIs) have drastically changed the outcome of chronic myeloid leukemia (CML) patients. However, a subset of patients experienced resistance and/or intolerance and need to switch to other agents. Resistance to second-generation TKIs used in first-line treatment is less of an issue when compared to imatinib in first line. New drugs that are able to improve efficacy, without long-term off-target effects are needed. Allosteric inhibitors such as asciminib (ABL001) were created to overcome resistance and off-target toxicity. Areas covered: In this review, we report the mechanism of action, pharmacokinetic data, and the clinical trial results of asciminib tested in chronic phase CML patients. Expert Opinion: Asciminib, the first example of allosteric inhibition, could be a promising approach as third-line therapy and in the subset of patients with T315I mutation that, for coexistent comorbidities, cannot receive other drugs. Future results will probably help to move the drug to earlier lines of treatment.

Automated summary

Tyrosine kinase inhibitors (TKIs) have significantly improved outcomes for CML patients, but resistance and intolerance can still be issues. Asciminib, an allosteric inhibitor, shows promise as a third-line treatment option, particularly for patients with the T315I mutation.