Clinical benefit of glasdegib plus low-dose cytarabine in patients with de novo and secondary acute myeloid leukemia: long-term analysis of a phase II randomized trial

Michael Heuser, B. Douglas Smith, Walter Fiedler, Mikkael A. Sekeres, Pau Montesinos, Brian Leber, Akil Merchant, Cristina Papayannidis, José A. Pérez-Simón, Caroline J. Hoang, Thomas O’Brien, Weidong Wendy Ma, Mirjana Zeremski, Ashleigh O’Connell, Geoffrey Chan, Jorge E. Cortes

Research output: Contribution to journalArticlepeer-review

Abstract

This analysis from the phase II BRIGHT AML 1003 trial reports the long-term efficacy and safety of glasdegib + low-dose cytarabine (LDAC) in patients with acute myeloid leukemia ineligible for intensive chemotherapy. The multicenter, open-label study randomized (2:1) patients to receive glasdegib + LDAC (de novo, n = 38; secondary acute myeloid leukemia, n = 40) or LDAC alone (de novo, n = 18; secondary acute myeloid leukemia, n = 20). At the time of analysis, 90% of patients had died, with the longest follow-up since randomization 36 months. The combination of glasdegib and LDAC conferred superior overall survival (OS) versus LDAC alone; hazard ratio (HR) 0.495; (95% confidence interval [CI] 0.325–0.752); p = 0.0004; median OS was 8.3 versus 4.3 months. Improvement in OS was consistent across cytogenetic risk groups. In a post-hoc subgroup analysis, a survival trend with glasdegib + LDAC was observed in patients with de novo acute myeloid leukemia (HR 0.720; 95% CI 0.395–1.312; p = 0.14; median OS 6.6 vs 4.3 months) and secondary acute myeloid leukemia (HR 0.287; 95% CI 0.151–0.548; p < 0.0001; median OS 9.1 vs 4.1 months). The incidence of adverse events in the glasdegib + LDAC arm decreased after 90 days’ therapy: 83.7% versus 98.7% during the first 90 days. Glasdegib + LDAC versus LDAC alone continued to demonstrate superior OS in patients with acute myeloid leukemia; the clinical benefit with glasdegib + LDAC was particularly prominent in patients with secondary acute myeloid leukemia. ClinicalTrials.gov identifier: NCT01546038.

Original languageEnglish (US)
Pages (from-to)1181-1194
Number of pages14
JournalAnnals of Hematology
Volume100
Issue number5
DOIs
StatePublished - May 2021

Keywords

  • Acute myeloid leukemia
  • Clinical trial
  • Glasdegib
  • Secondary acute myeloid leukemia

ASJC Scopus subject areas

  • Hematology

Fingerprint

Dive into the research topics of 'Clinical benefit of glasdegib plus low-dose cytarabine in patients with de novo and secondary acute myeloid leukemia: long-term analysis of a phase II randomized trial'. Together they form a unique fingerprint.

Cite this