15 April 2019

An inhibitor that targets a specific mutation in relapsed or refractory acute myeloid leukaemia improves the survival rate of patients, a major conference has been told.

The phase III ADMIRAL trial, led by a team at the Abramson Cancer Center of the University of Pennsylvania, USA, has revealed that patients with a mutation in the Fms-like tyrosine kinase 3 (FLT3) gene lived twice as long if they took gilteritinib (a FLT3 inhibitor), compared to those who received chemotherapy.

Dr Alexander Perl, who presented the findings at the 2019 American Association for Cancer Research Annual Meeting in Atlanta, Georgia, USA, said “patients with FLT3 mutations who have relapsed or refractory AML have very low response rates to chemotherapy at the time of relapse, and their survival is poor as a result".

“This drug is specifically designed to help this group of patients, and now we've shown it can make a huge difference for those who, until recently, had no specific therapies available beyond chemotherapy.”

FLT3 is the most commonly mutated gene in AML, with mutations found in the leukaemia cells of about a third of patients. It is normally expressed in normal bone marrow cells and regulates the orderly growth of blood cells in response to daily demands. However, when the gene is mutated in leukaemia, the cancer cells grow in an uncontrolled manner. A drug such as gilteritinib, marketed as Xospata, switches off the function of FLT3.

This trial involved 371 patients, 247 of whom who were randomly selected to receive gilteritinib, with the remaining 124 receiving clinician’s choice of chemotherapy.

Researchers established that the patients who took gilteritinib had a median overall survival of 9.3 months compared with 5.6 months for the chemotherapy patients.

At one year, 37.1% of patients on gilteritinib were still alive, compared to 16.7% of patients in the chemotherapy group. The combined rates of complete remissions (CR) or CR with partial haematologic recovery (CRh) were 34% for the gilteritinib group and 15% for the chemotherapy arm.

“Across the board, this trial shows gilteritinib carries a clear survival benefit, meaning we now have a targeted, highly-effective, and well-tolerated treatment option for a group of truly high-risk patients,” said Dr Perl.

“Although the incidence of various side effects was similar across the study arms, patients took gilteritinib for considerably longer than they underwent chemotherapy.

“This actually means the likelihood of side effects on a daily basis is lower on this drug, and this favourable side effect profile allowed us to give gilteritinib as an outpatient treatment, a huge shift for these patients.”

Following the success of the ADMIRAL trial, multi-centre clinical trials have begun testing gilteritinib in combination with other therapies for relapsed or refractory FLT3­-mutated AML, as well as frontline therapy for newly diagnosed patients.




AACR Annual Meeting: https://www.aacr.org/Newsroom/Pages/News-Release-Detail.aspx?ItemID=1295

Presentation abstract: https://www.abstractsonline.com/pp8/#!/6812/presentation/9835