Glasdegib combined with chemotherapy in the treatment of patients with acute myeloid leukemia: a comprehensive meta-analysis.

Abstract

Background: Acute myeloid leukemia (AML) is characterized by clonal expansion of myeloid precursors, often accompanied by poor prognostic outcomes in older populations due to molecular heterogeneity and resistance to conventional chemotherapeutic agents. Glasdegib, a potent inhibitor of the Hedgehog signaling pathway, has emerged as a targeted agent that enhances chemosensitivity and demonstrates favorable pharmacodynamic profiles in combination regimens. This systematic review evaluates the clinical efficacy and safety of Glasdegib-based therapies in the management of AML.

Methods: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched four electronic databases (PubMed, Scopus, Cochrane Library, and Web of Science) to identify eligible studies reported up to August 2024. Using R version R.4.4.1, we reported outcomes as pooled proportions and confidence intervals (CIs). The survival data were extracted from Kaplan-Meier curves and reconstructed.

Results: The pooled two-year overall survival for Glasdegib plus chemotherapy was 30% (95% CI [27-34%], I² = 0%). Subgroup analysis showed rates of 36% (95% CI [30-42%], Cytarabine and Daunorubicin), 27% (95% CI [20-36%], Low-Dose Cytarabine), and 25% (95% CI [20-31%], Azacitidine. Median survival times were highest for Glasdegib plus Cytarabine and Daunorubicin at 17.6 months (95% CI [15.6-21.9]), followed by 10.4 months (95% CI [8.22-12.3]) for Glasdegib plus Azacitidine, and 7.89 months (95% CI [5.47-11.5]) for Glasdegib plus Low-Dose Cytarabine. Safety analysis revealed varied adverse event rates for Glasdegib plus chemotherapy, with febrile neutropenia (37%), nausea (47%), vomiting (32%), and QT prolongation (44%) being the most commonly reported.

Conclusion: Glasdegib combined with chemotherapy demonstrates promising efficacy in improving survival outcomes for AML patients, particularly in combination with Cytarabine and Daunorubicin. While adverse events were common, they were generally manageable, supporting Glasdegib as a viable therapeutic option. Further research is warranted to optimize treatment regimens and evaluate long-term safety and quality-of-life outcomes.