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Leukemia. 2019 Feb;33(2):379-389. doi: 10.1038/s41375-018-0312-9. Epub 2018 Dec 16.

Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome.

Author information

1
Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX, USA. jcortes@mdanderson.org.
2
Otto-von-Guericke University Medical Center, Magdeburg, Germany.
3
Internal Medicine II, University Hospital Jena, Jena, Germany.
4
Department of Haematology and Transplantology, Medical University of Gdańsk, Gdańsk, Poland.
5
Department of Hematology and Oncology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
6
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
7
Department of Hematology, Medical University of Lodz, Lodz, Poland.
8
Hospital Universitari i Politècnic La Fe, Valencia, Spain.
9
CIBERONC, Instituto Carlos III, Madrid, Spain.
10
Division of Hematology, University of Colorado School of Medicine, Aurora, CO, USA.
11
Hôpital Charles LeMoyne, Greenfield Park, QC, Canada.
12
Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK.
13
Pfizer Oncology, New York, NY, USA.
14
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.

Abstract

Glasdegib is a Hedgehog pathway inhibitor. This phase II, randomized, open-label, multicenter study (ClinicalTrials.gov, NCT01546038) evaluated the efficacy of glasdegib plus low-dose cytarabine (LDAC) in patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome unsuitable for intensive chemotherapy. Glasdegib 100 mg (oral, QD) was administered continuously in 28-day cycles; LDAC 20 mg (subcutaneous, BID) was administered for 10 per 28 days. Patients (stratified by cytogenetic risk) were randomized (2:1) to receive glasdegib/LDAC or LDAC. The primary endpoint was overall survival. Eighty-eight and 44 patients were randomized to glasdegib/LDAC and LDAC, respectively. Median (80% confidence interval [CI]) overall survival was 8.8 (6.9-9.9) months with glasdegib/LDAC and 4.9 (3.5-6.0) months with LDAC (hazard ratio, 0.51; 80% CI, 0.39-0.67, P = 0.0004). Fifteen (17.0%) and 1 (2.3%) patients in the glasdegib/LDAC and LDAC arms, respectively, achieved complete remission (P < 0.05). Nonhematologic grade 3/4 all-causality adverse events included pneumonia (16.7%) and fatigue (14.3%) with glasdegib/LDAC and pneumonia (14.6%) with LDAC. Clinical efficacy was evident across patients with diverse mutational profiles. Glasdegib plus LDAC has a favorable benefit-risk profile and may be a promising option for AML patients unsuitable for intensive chemotherapy.

PMID:
30555165
PMCID:
PMC6365492
DOI:
10.1038/s41375-018-0312-9
[Indexed for MEDLINE]
Free PMC Article

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