glasdegib + cytarabine + daunorubicin

Glasdegib + cytarabine + daunorubicin is a combination regimen investigated for the treatment of adults with previously untreated acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS)[1][3][4][7]. Glasdegib is a small molecule inhibitor of the Hedgehog signaling pathway, which is implicated in leukemic stem cell survival. Cytarabine is a nucleoside analog that inhibits DNA synthesis, and daunorubicin is an anthracycline that intercalates DNA and inhibits topoisomerase II, leading to cytotoxicity. In this combination, glasdegib is administered orally, typically 100 mg daily, alongside standard intravenous induction therapy with cytarabine (continuous infusion, days 1–7) and daunorubicin (days 1–3). The goal is to improve remission and survival in AML by combining targeted and cytotoxic mechanisms. Phase 2 and phase 3 studies have shown the regimen to be well tolerated and to have encouraging activity, although the phase 3 BRIGHT AML 1019 trial did not demonstrate significant improvement in overall survival over standard intensive chemotherapy[2][5].