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Gilteritinib prolongs overall survival in patients with FLT3-mutated relapsed/refractory AML

Presented by
Dr Alexander Perl, University of Pennsylvania, USA
EHA 2019
Phase 3, ADMIRAL
Dr Alexander Perl (University of Pennsylvania, USA) presented the data from the phase 3 ADMIRAL trial of gilteritinib, a selective FLT3 inhibitor, for relapsed or refractory (R/R) acute myeloid leukaemia (AML). Patients were randomised 2:1 to receive either gilteritinib or one of 4 standard salvage chemotherapy treatments. The investigators report favourable outcomes of gilteritinib observed in this trial with increased complete response rate and improved overall survival for R/R AML [1].

FLT3 mutations (FLT3MUT+) occur in approximately 30% of patients with AML and are often associated with poor survival. Results from the ADMIRAL trial show the median overall survival for R/R FLT3MUT+ AML patients who received gilteritinib was 9.3 months vs 5.6 months for patients who received salvage chemotherapy (HR 0.637; 95% CI 0.490-0.830; P=0.007); 1-year survival rates were 37% for patients who received gilteritinib vs 17% for patients who received salvage chemotherapy (see Table).

Table: The gilteritinib arm had superior response rates across all 4 major co-mutation cohorts in the ADMIRAL trial

ITT, intention to treat; CR/CRh, complete remission/with partial haematological recovery; SC, salvage chemotherapy; HR, hazard ratio. Permission granted by Dr Perl to use abbreviated Table.

The most common treatment-emergent adverse events of any grade occurring in ≥10% of patients during the first 30 days of treatment with gilteritinib were anaemia (33%), increased transaminases (24%), febrile neutropenia (21%), thrombocytopenia (19%), constipation (17%), pyrexia (15%), fatigue (15%), decreased neutrophil count (14%), increased blood alkaline phosphatase (13%), nausea (13%), hypokalaemia (11%), cough (11%), headache (10%), and diarrhoea (10%).

Dr Perl concluded that the clinical benefit of gilteritinib was maintained regardless of the presence of NPM1, DNMT3A, or WT1 co-mutations (see Table). Relative to the other co-mutated cohorts, patients with both NPM1 and DNMT3A co-mutations had the greatest survival benefit with gilteritinib. “We are very encouraged by the findings of the ADMIRAL trial,” said Dr Perl. “Patients with relapsed/refractory FLT3 mutation-positive AML generally have a poor prognosis and short survival. Until just recently, they had few treatment options.” This experimental therapy is an oral drug that can be given on an outpatient basis, while salvage chemotherapy patients mostly are admitted for a couple of weeks in the hospital. Even if the outcome would have been equal, it offers an enormous advantage for the patient. “These findings are practice changing for this patient population.”

    1. Perl A et al. Abstract S876. 24th Congress of the EHA, 13-16 June 2019, Amsterdam, the Netherlands.


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