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

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

Fecha de publicación:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Cortes, JE
  • Heidel, FH
  • Hellmann, A
  • Fiedler, W
  • Smith, BD
  • Robak, T
  • Pollyea, DA
  • DesJardins, P
  • Ottmann, O
  • Ma, WW
  • Shaik, MN
  • Laird, AD
  • Zeremski, M
  • O'Connell, A
  • Chan, G
  • Heuser, M

Grupos

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.

Datos de la publicación

ISSN/ISSNe:
0887-6924, 1476-5551

LEUKEMIA  SPRINGERNATURE

Tipo:
Article
Páginas:
379-389
PubMed:
30555165
Factor de Impacto:
3,966 SCImago ℠
Cuartil:
Q1 SCImago ℠

Citas Recibidas en Web of Science: 398

Documentos

  • No hay documentos

Métricas

Filiaciones mostrar / ocultar

Campos de Estudio

Compartir