Abstract
Acute myeloid leukemia (AML) is an aggressive hematologic malignancy primarily affecting older adults. Historically, the highest rates of response have been achieved with intensive induction chemotherapy; however, a significant portion of older or unfit adults with AML are unable to tolerate intensive therapy or have chemotherapy-resistant disease, creating a large need for active and less intensive treatment strategies. Glasdegib, an oral inhibitor of the transmembrane protein Smoothened (SMO) involved in the Hedgehog (Hh) signaling pathway, was approved in 2018 for older or unfit adults with AML and attained a role in clinical practice after showing an overall survival (OS) advantage when combined with the established agent low-dose cytarabine (LDAC). Since that time, however, several other highly active lower intensity therapies such as venetoclax plus a hypomethylating agent (HMA) have garnered a dominant role in the treatment of this patient population. In this review, we summarize the role of glasdegib in the current treatment landscape of newly diagnosed AML and discuss ongoing investigations into its role in novel combination therapies.