The efficacy and safety of Asciminib in the treatment of Chronic Myeloid Leukemia: A systematic review and meta-analysis

Abstract

Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of the BCR :ABL1 fusion gene, which drives leukemogenesis through aberrant tyrosine kinase activity. While first- and second-generation tyrosine kinase inhibitors (TKIs) have transformed the management of CML, treatment failure due to resistance or intolerance—especially in patients with the T315I mutation—remains a critical concern. Asciminib, a first-in-class STAMP inhibitor targeting the myristoyl pocket of ABL1, offers a novel therapeutic approach distinct from ATP-competitive TKIs. This systematic review summarizes current evidence on the efficacy and safety of Asciminib in adults with CML who have failed at least two prior TKIs. Data from eight clinical trials involving 1,093 patients revealed that Asciminib demonstrated superior major molecular response rates compared to Bosutinib and Ponatinib in patients without the T315I mutation, along with a favorable safety profile marked by fewer grade ≥3 adverse events and treatment discontinuations. However, its efficacy in T315I-mutant CML remains inconclusive and warrants further investigation. The unique mechanism of Asciminib and its tolerability profile support its clinical utility as a third-line agent in CML, with potential future applications in combination therapies and treatment-free remission strategies.