Clinical efficacy and safety of asciminib in chronic myeloid leukemia-chronic phase (CML-CP) in real-world settings: a systematic literature review

Abstract

Abstract

In the treatment of chronic myeloid leukemia (CML), significant unmet needs persist, particularly for patients with CML in chronic phase (CP) who develop treatment resistance or intolerance. Asciminib, the first allosteric inhibitor specifically targeting the ABL1 myristoyl pocket, represents a novel therapeutic option that has gained approval from the Food and Drug Administration and the European Medicines Agency for use in patients with CML-CP. A systematic literature review was conducted using Embase ® , MEDLINE ® , and Cochrane databases to evaluate the clinical efficacy and safety of asciminib in patients with ≥ 2 prior treatment lines in a real-world setting. Twenty-two studies, with sample sizes ranging from 12 to 394, were identified. The complete cytogenetic response rates (CCyR) reported across the studies varied widely from 8% to 73%. Findings indicate that patients achieved favorable molecular responses: major molecular response (MMR) rates ranged from 17 to 67%, with higher rates in ponatinib-naïve (65% vs. 10% in ponatinib pre-treated patients) and TKI-intolerant patients (up to 80%). Patients with T315I mutations showed a gradual improvement in MMR over time. Overall survival ranged from 73 to 100% at follow-up. Adverse events (AEs) were manageable, with thrombocytopenia, fatigue, and rash as the most frequent; discontinuations due to AEs occurred in ≤ 16% of patients. Real-world evidence confirms that asciminib is a valuable therapeutic option for pre-treated CML-CP patients, demonstrating favorable efficacy and a manageable safety profile.