EHA 2019 – Gilteritinib, a new treatment paradigm for relapsed/refractory acute myeloid leukaemia

  • Elena Riboldi — Agenzia Zoe
  • Univadis
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  • Single agent oral gilteritinib improved response and survival in patients with FLT3-mutated relapsed/refractory (R/R) acute myeloid leukemia (AML) compared with parenteral salvage chemotherapy (SC).


Why this matters

  • Patients with R/R AML have a poor response to SC.
  • FLT3 mutations confer an increased risk for early relapse and poor survival.
  • Based upon response rates from the ADMIRAL phase 3 study gilteritinib became the first FLT3 inhibitor approved as single-agent therapy in this population.


Study design

  • The phase 3 ADMIRAL trial enrolled 371 adult patients with confirmed FLT3mut+ AML refractory to induction chemotherapy or in untreated first relapse.
  • Patients were randomly assigned (2:1) to receive gilteritinib or a pre-randomization selected standard SC regimen.
  • The co-primary endpoints in the intention-to-treat analysis were overall survival (OS) and the combined rate of complete remission/complete remission with partial hematologic recovery (CR/CRh).


Key results

  • OS was significantly longer in the gilteritinib arm than in the SC arm (9.3 vs 5.6 months; HR 0.637; P=0.0007).
  • The 12-months survival rate was 37.1% (95%CI 31%-44%) in the gilteritinib arm and 16.7% (95%CI 10%-25%) in the SC arm.
  • The CR/CRh rates for gilteritinib and SC were 34.0% and 15.3%, respectively.
  • Patients in the gilteritinib arm who resumed gilteritinib (n=35) after hematopoietic stem cell transplantation (HSCT) had a better OS compared to patients (n=16) who did not resume the drug (16.2 months vs 8.4 months; HR 0.387 [95%CI 0.164-0.915; P=0.024).
  • Common grade ≥3 AEs related to gilteritinib were anaemia (19.5%), febrile neutropenia (15.4%), thrombocytopenia (12.2%), and decreased platelet count (12.2%).



  • The effect of maintenance therapy post-HSCT was studied in a small number of patients.



  • Astellas Pharma Inc.


Expert commentary

  • “Gilteritinib has been approved based on the results of this study and because of this we have a new standard of care for this population. These data argue for testing for FLT3 mutations at the time of relapse and for the use of targeted therapy over standard chemotherapy in this group.  Compared with salvage chemotherapy, gilteritinib was generally associated with lower toxicity in the first 30 days of treatment, which facilitated outpatient administration of the drug.” Alexander E. Perl, MD, Abramson Cancer Center, University of Pennsylvania, investigator of the ADMIRAL trial.