A systematic review on Asciminib: could it replace conventional tyrosine kinaseinhibitors (TKIs) in patients with chronic myeloid leukemia?

Background: Asciminib, a newer therapy for BCR::ABL۱, was approved for treatingpatients with chronic myeloid leukemia (CML) in the chronic phase and patients over ۱۸years old who had more than two previous therapies, including those with T۳۱۵Imutation. Asciminib is an allosteric inhibitor that binds to a myristoylic site of the BCRABL۱protein and immobilizes it in an inactive state through a mechanism distinct fromother ABL kinase inhibitors. Due to the distinctive binding site of asciminib, it cansurmount mutations that confer resistance to conventional tyrosine kinase inhibitors(TKIs) like T۳۱۵I which is positioned at the ATP-binding site of BCR::ABL۱. In thissystematic review, we investigate whether Asciminib can replace conventional TKIs.Methods and material: This study was performed by using the collected articles inEnglish that were available on details of the main topic in Scopus, PubMed, and Web ofScience with keywords chronic myeloid leukemia, Asciminib, TKI, tyrosine kinaseinhibitor, all in title/abstract field. This study was performed based on the PRISMAguideline and articles were selected based on the exclusion and inclusion criteria.Results: After excluding duplicated papers, ۱۳۲ studies were admitted to the screeningstep. Finally, ۱۱ studies were entered into the study. Among patients with chronic phase-CML accompanied by T۳۱۵I mutation, ۹۰% with a hematologic relapse had a completehematologic response (CHR); ۴۸% without a complete cytogenetic response had acomplete cytogenetic response (CCYR). A major molecular response (MMR) wasachieved by ۱۲ months in ۳۶% of patients. Among patients with chronic phase-CMLwithout T۳۱۵I mutation, ۹۱% with a hematologic relapse had a CHR; ۵۷% without acomplete cytogenetic response had a CCYR, and ۴۶% achieved MMR by ۱۲ months.Conclusion: Asciminib can replace conventional TKIs due to its low toxicity, morespecificity, and more effective induction of CHR, CCYR, and MMR.

کلیدواژه ها:

chronic myeloid leukemia ، Asciminib ، TKI ، tyrosine kinase inhibitor