Gilteritinib Provides Long-Term Benefit in Rel/Ref FLT3-Mutated Acute Myeloid Leukemia

Gilteritinib may improve long-term outcomes, compared with salvage chemotherapy, in patients with relapsed/refractory FLT3-mutated acute myeloid leukemia (AML), according to updated data from the ADMIRAL trial published in Blood. [1]

The phase 3 ADMIRAL trial ( Identifier: NCT02997202) enrolled adults with FLT3-mutated AML who were in their first relapse after induction or were refractory to induction therapy. The patients were randomly assigned 2:1 to receive gilteritinib at 120 mg/day or preselected high- or low-intensity salvage chemotherapy.

The primary analysis of ADMIRAL demonstrated superiority of gilteritinib over salvage chemotherapy. [2] Researchers conducted a post hoc analysis 2 years after the primary analysis to characterize the long-term treatment effects and safety of gilteritinib beyond 1 year. [1]

At a median follow-up of 37.1 months, there were 203 deaths (82%) in the gilteritinib arm and 97 deaths (78%) in the salvage chemotherapy arm.

There were 49 patients in the gilteritinib arm who were alive for at least 2 years, and 26 of them had not relapsed for at least 2 years. Of the 26 patients, 18 had undergone hematopoietic stem cell transplant (HSCT), and 16 had restarted gilteritinib as post-HSCT maintenance therapy.

Patients in both treatment arms went on to HSCT or to receive tyrosine kinase inhibitors, with or without chemotherapy, after stopping study treatment.

The median overall survival (OS) was 9.3 months in the gilteritinib arm and 5.6 months in the salvage chemotherapy arm (hazard ratio [HR], 0.67; 95% CI, 0.52-0.85; P =.0013). The 2-year OS rates were 20.6% and 14.2%, respectively.

With extended follow-up, the survival benefit of gilteritinib was maintained in the FLT3-ITD mutation subgroup and in patients with a high FLT3-ITD allelic ratio but not in the FLT3-TKD mutation subgroup or in patients with a low FLT3-ITD allelic ratio.

The 2-year cumulative relapse rate was 52.6% in gilteritinib-treated patients who achieved a best response of complete remission and 75.5% in those who achieved a best response of composite complete remission (CRc). Most relapses after CRc in the gilteritinib arm occurred within 12 months of enrollment, and relapses were rare after 18 months.

The most common adverse event (AE) of interest in the gilteritinib arm during the first and second year of follow-up were increased levels of liver transaminases, which decreased during year 2. AEs of interest leading to gilteritinib dose reductions were observed in 5.7% of patients.

During the second year of follow-up, cardiac AEs of interest in the gilteritinib arm included cardiorespiratory arrest (n=1), ventricular tachycardia (n=1), and pericardial effusion (n=1). None of these events were fatal.

Disclosures: This research was supported by Astellas Pharma, Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


  1. 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. Blood. Published online January 26, 2022. doi:10.1182/blood.2021011583
  2. Perl AE, Martinelli G, Cortes JE, et al. Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML. N Engl J Med. 2019; 381:1728-1740. doi:10.1056/NEJMoa1902688