An evaluation of glasdegib for the treatment of acute myelogenous leukemia

ABSTRACT

Introduction

Despite recent advances in the treatment of adult acute myelogenous leukemia (AML), the overall outcome remains dismal especially in high-risk AML patients, including the elderly and the relapsed/refractory populations. In this setting, various clinical trials have recently explored novel therapeutic agents either used alone or in combination with intensive chemotherapy or low-intensity treatments.

Areas covered

The current paper reviews the clinical development of glasdegib, a selective inhibitor of the Hedgehog signaling pathway through binding to its target SMO, for the treatment of AML.

Expert opinion

Glasdegib confirmed its efficacy and showed an acceptable tolerability, especially when used in combination either with ‘3 + 7ʹ chemotherapy or with low-intensity therapies. In 2018, glasdegib was approved by the Food and Drug Administration (FDA) in combination with low-dose cytarabine for the treatment of newly diagnosed AML in patients older than 75 years or presenting with severe comorbidities.

KEYWORDS:

• Acute myeloid leukemia
• elderly
• treatment
• new agents
• SMO inhibitor
• Hedgehog signaling

Article highlights

• Glasdegib is a potent inhibitor of the Hedgehog signaling pathway acting through binding to its target SMO.

• Glasdegib has also shown a repealed effect on leukemia stem cells through a downstream Gli2 inhibition.

• Combined with standard chemotherapy or low-intensity therapies, glasdegib showed efficacy and tolerability in the treatment of acute myeloid leukemia and appears as a promising new treatment strategy.

• Glasdegib was recently approved by the FDA in combination with low-dose cytarabine for the treatment of elderly patients with acute myeloid leukemia.

Declaration of interest

X Thomas has consulted for and had an advisory role with AbbVie, Celgene, Sunesis Pharmaceuticals, Amgen Inc., Daiichi Sankyo, Astellas and Incyte. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.