Glasdegib in newly diagnosed acute myeloid leukemia.
Expert Rev Anticancer Ther
; 21(6): 573-581, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-33593233
ABSTRACT
INTRODUCTION:
Acute myeloid leukemia (AML) is an aggressive blood cancer that proves fatal for the majority of affected individuals. Older patients are particularly vulnerable due to more unfavorable disease biology and diminished ability to tolerate intensive induction chemotherapy (ICT). Safer, more efficacious therapies are desperately needed. AREAS COVERED We briefly summarize the challenges facing AML treatment and introduce the rapidly expanding therapeutic landscape. Our focus is on the Hedgehog (Hh) pathway and how preclinical evidence has spurred the clinical development of selective inhibitors for oncology indications. Glasdegib is the first Hh pathway inhibitor approved for the treatment of a hematologic malignancy, and we review its pharmacology, safety, efficacy, and potential clinical impact in AML patients. EXPERT OPINION Advances in the mechanistic understanding of AML have started to translate into improved therapeutic options for patients with contraindications to ICT. Glasdegib improved overall survival in this population when combined with low-dose cytarabine. While an encouraging development for these difficult to treat patients, alternative combination therapy approaches such as venetoclax plus azacitidine have gained greater clinical traction. Further investigation of glasdegib combination strategies and predictive biomarkers, particularly in regard to overcoming chemoresistance and preventing relapse, is needed to better define its clinical utility.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Leucemia Mieloide Aguda
/
Proteínas Hedgehog
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article