An evaluation of asciminib for patients with chronic myeloid leukemia previously treated with ≥2 tyrosine kinase inhibitors

Introduction: To date, five tyrosine kinase inhibitors (TKIs) are available for treating chronic myeloid leukemia (CML) patients in clinical practice. Despite this, a significant proportion of patients will ultimately develop failure to approved TKIs due to intolerance or resistance. Consequently, new treatment approaches are still required in this unmet clinical need. Asciminib, a first-in-class BCR:: ABL1 inhibitor Specifically Targeting the ABL Myristoyl Pocket (STAMP), has the potential to overcome resistance/intolerance to prior TKI treatment. Areas covered: This review will cover the mechanism of action, pharmacokinetic profile, and clinical data of asciminib based on available information from laboratory studies, clinical trials, and real-world evidence. Expert opinion: Recent approval of asciminib will require positioning of this drug in the treatment algorithm of CML patients failing initial TKI therapy. Available data support the lack of cross-intolerance of asciminib with other TKIs and its favorable cardiovascular toxicity profile. In addition, asciminib has demonstrated considerable efficacy in CML patients who have failed at least two TKIs, although preliminary data suggest that this efficacy may be lower in those previously exposed to ponatinib. The introduction of asciminib in clinical practice may represent an important step forward in the management of CML.