Gilteritinib maintenance improves overall survival in relapsed /refractory FLT3+ AML

June 2022 Clinical trials Nalinee Pathak
AML Acute Myeloid Leukemia acronym on colorful wooden cubes

The results from the ADMIRAL study report that continued and post-transplant gilteritinib maintenance therapy leads to better long term survival and sustained remission in patients with relapsed or refractory FLT3-mutation-positive (FLT3+) acute myeloid leukaemia (AML). The findings of this trial were published in the journal Blood.

After the primary analysis, the current study was a posthoc analysis of the two years data phase III ADMIRAL trial. The main aim of the investigation was to determine the long-term efficacy and safety of gilteritinib in patients with refractory/relapsed FLT3+ AML.

The ADMIRAL Phase III study enrolled FLT3+ AML patients who were either in their first relapse following complete remission with initial induction therapy or who were refractory to their initial induction treatment. Participants were randomly assigned (2:1) to either receive gilteritinib 120 mg/day (n=247) or preselected high- or low-intensity salvage chemotherapy (SC)  (n=124).

Key findings

After a median follow-up of 37.1 months, deaths were reported in 203/247 and 97/124 patients in the gilteritinib and control. The median overall survival (OS) was prolonged in the gilteritinib arm (9.3 months) as compared to the SC treatment (5.6 months, hazard ratio = 0.665; 95% CI 0.518-0.853; two-sided p=0.0013). The two-year estimated survival rates were higher for gilteritinib (20.6%, 95% CI 15.8-26.0) than SC (14.2%, 95% CI 8.3-21.6).

The two years, cumulative incidence of relapse after composite complete remission was 75.7% in the gilteritinib arm. Few relapses were observed after 18 months of enrollment in the study. 49 and 14 patients were alive in the gilteritinib and SC arm for ≥2 years, respectively.

Adverse events

The most common adverse events were increased liver transaminase during the first and second years of gilteritinib therapy. Overall, the gilteritinib treatment had a stable safety profile.

The findings are the first evidence that an FLT3 inhibitor in a salvage setting provides survival benefits over SC in patients with relapsed or refractory FLT3+ AML.


Perl AE, Larson RA, Podoltsev NA, et al. Follow-up of patients with R/R FLT3-mutation-positive AML treated with gilteritinib in the phase 3 ADMIRAL trial [published online ahead of print, 2022 Jan 26]. Blood