Asciminib in chronic myeloid leukemia: Superior efficacy and favorable safety outcomes from a systematic review and meta-analysis

Abstract Introduction: Asciminib is a novel allosteric inhibitor targeting the myristoyl pocket of the BCR:ABL1 protein in patients with chronic myeloid leukemia (CML). This study evaluates the efficacy, safety, and tolerability of asciminib in patients with chronic-phase CML (CML-CP), both newly diagnosed and previously treated with tyrosine kinase inhibitors (TKIs). Methods: A systematic search of Cochrane CENTRAL, Ovid Medline R, PubMed, and Web of Science databases up to 13 May 2025, was conducted. RCTs directly comparing asciminib with control groups were included. Inverse variance-weighted random-effects model were utilized for the main analysis. The primary outcome was major molecular response (MMR) rate at during follow-up, primary safety outcome was the incidence of any grade ≥ 3 adverse events (AEs). Results: Three RCTs comprising 701 patients with a follow-up duration of 24–96 weeks were included. Asciminib significantly increased MMR rates during follow-up compared to controls (mean difference [MD] 1.45, 95% confidence interval [CI] 1.19 to 1.76, I²=5.2%, p=0.0003). Regarding safety, asciminib was associated with a significantly lower risk of grade ≥3 AEs overall (RR=0.76, 95% CI 0.63–0.92; p=0.0045), including anemia (RR=0.28, 95% CI 0.09–0.82; p=0.021), diarrhea (RR=0.09, 95% CI 0.01–0.56; p=0.011), elevated AST (RR=0.13, 95% CI 0.03–0.60; p=0.009), and elevated ALT (RR=0.13, 95% CI 0.02–0.69; p=0.017) compared with second-generation TKIs. No significant differences were observed for neutropenia (RR=0.83, 95% CI 0.39–1.79; p=0.63). Asciminib showed nonsignificant trends toward increased risks of thrombocytopenia (RR=1.45, 95% CI 0.59–3.55; p=0.41), upper respiratory tract infection (RR=1.65, 95% CI 0.10–26.43; p=0.72), vomiting (RR=2.19, 95% CI 0.14–33.30; p=0.57), nausea (RR=1.65, 95% CI 0.10–26.43; p=0.72), and headache (RR=3.75, 95% CI 0.29–48.74; p=0.31). Conclusion: Asciminib significantly improved MMR during follow-up compared to the control group and and demonstrates a favorable safety profile, with a reduced risk of grade ≥3 AEs compared with second-generation TKIs. Subgroup analyses will be performed based on asciminib dose and prior use of TKIs for the primary outcome.