GILTERITINIB SIGNIFICANTLY PROLONGS OVERALL SURVIVAL IN PATIENTS WITH FLT3-MUTATED (FLT3MUT+) RELAPSED/REFRACTORY (R/R) ACUTE MYELOID LEUKEMIA (AML): RESULTS FROM THE PHASE 3 ADMIRAL TRIAL
Author(s): ,
Alexander Perl
Affiliations:
Abramson Cancer Center,University of Pennsylvania,Philadelphia,United States
,
Giovanni Martinelli
Affiliations:
Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRST IRCCS,Medola,Italy
,
Jorge Cortes
Affiliations:
MD Anderson Cancer Center,University of Texas,Houston,United States
,
Andreas Neubauer
Affiliations:
Universitätsklinikum Giessen und Marburg GmbH,Marburg,Germany
,
Ellin Berman
Affiliations:
Memorial Sloan-Kettering Cancer Center,New York,United States
,
Stefania Paolini
Affiliations:
L. and A. Seràgnoli Institute of Hematology,Bologna University Medical School,Bologna,Italy
,
Pau Montesinos
Affiliations:
Hospital Universitari i Politècnic La Fe, Valencia & CIBERONC,Instituto Carlos III,Madrid,Spain
,
Maria Baer
Affiliations:
University of Maryland Greenebaum Comprehensive Cancer Center,Baltimore,United States
,
Richard Larson
Affiliations:
University of Chicago,Chicago,United States
,
Celalettin Ustun
Affiliations:
University of Minnesota,Minneapolis,United States
,
Francesco Fabbiano
Affiliations:
Ospedali Riuniti Villa Sofia-Cervello,Palermo,Italy
,
Antonio Di Stasi
Affiliations:
University of Alabama at Birmingham,Birmingham,United States
,
Robert Stuart
Affiliations:
Hollings Cancer Center,Medical University of South Carolina,Charleston,United States
,
Rebecca Olin
Affiliations:
University of California San Francisco,San Francisco,United States
,
Margaret Kasner
Affiliations:
Thomas Jefferson University,Philadelphia,United States
,
Fabio Ciceri
Affiliations:
IRCCS San Raffaele Scientific Institute,Milano,Italy
,
Wen-Chien Chou
Affiliations:
National Taiwan University,Taipei City,Taiwan, Province of China
,
Nikolai Podoltsev
Affiliations:
Yale University School of Medicine,New Haven,United States
,
Christian Recher
Affiliations:
Institut Universitaire du Cancer Toulouse - Oncopole,Cedex,France
,
Hisayuki Yokoyama
Affiliations:
Sendai Medical Center,National Hospital Organization,Sendai,Japan
,
Naoko Hosono
Affiliations:
University of Fukui,Fukui,Japan
,
Sung-Soo Yoon
Affiliations:
Seoul National University,Seoul,Korea, Republic Of
,
Je-Hwan Lee
Affiliations:
Asan Medical Center,University of Ulsan College of Medicine,Seoul,Korea, Republic Of
,
Timothy Pardee
Affiliations:
Wake Forest Baptist Medical Center,Winston-Salem,United States
,
Amir Fathi
Affiliations:
Massachussetts General Hospital,Harvard Medical School,Boston,United States
,
Chaofeng Liu
Affiliations:
Astellas Pharma Global Development,Northbrook,United States
,
Xuan Liu
Affiliations:
Astellas Pharma Global Development,Northbrook,United States
,
Erkut Bahceci
Affiliations:
Astellas Pharma Global Development,Northbrook,United States
Mark Levis
Affiliations:
Sidney Kimmel Comprehensive Cancer Center,Johns Hopkins University,Baltimore,United States
EHA Library. Perl A. Jun 15, 2019; 267459; S876
Alexander Perl
Alexander Perl
Contributions
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Abstract

Abstract: S876

Type: Oral Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 16:00 - 16:15

Location: Elicium 2

Background
Gilteritinib is a potent/selective oral inhibitor of fms-like tyrosine kinase 3 (FLT3). Based upon interim analysis response rates from the ADMIRAL phase 3 study of gilteritinib vs salvage chemotherapy (SC) in patients with R/R FLT3mut+ AML (NCT02421939), gilteritinib became the first FLT3 inhibitor approved as single-agent therapy in this population. 

Aims

We present the final results of the ADMIRAL trial. 

Methods
Adults with confirmed FLT3mut+ AML (FLT3-ITD and/or FLT3-TKD D835 or I836 mutations) refractory to induction chemotherapy or in untreated first relapse were randomized (2:1) to receive continuous 28-day cycles of 120 mg/day gilteritinib or pre-randomization selected SC: low-dose cytarabine (LoDAC), azacitidine (AZA), mitoxantrone/etoposide/cytarabine (MEC), or fludarabine/cytarabine/granulocyte colony-stimulating factor/idarubicin (FLAG-IDA). Prior FLT3 inhibitor use, other than midostaurin or sorafenib, was excluded. Overall survival (OS) and the combined rate of complete remission/complete remission with partial hematologic recovery (CR/CRh) were co-primary endpoints. Secondary endpoints were event-free survival (EFS) and CR rate; safety/tolerability was also examined.

Results
A total of 371 patients were randomized: 247 to gilteritinib and 124 to SC (MEC, 25.7%; FLAG-IDA, 36.7%; LoDAC, 14.7%; AZA, 22.9%). Median age was 62 years (range, 19–85). Baseline FLT3 mutations were: FLT3-ITD, 88.4%; FLT3-TKD, 8.4%; both FLT3-ITD and FLT3-TKD, 1.9%; unconfirmed, 1.3%. Overall, 39.4% of patients had refractory AML and 60.6% had relapsed AML. Patients randomized to gilteritinib had significantly longer OS (9.3 months) than SC (5.6 months; hazard ratio [HR] for death = 0.637; P=0.0007); 1-year survival rates were 37.1% and 16.7%, respectively. The CR/CRh rates for gilteritinib and SC were 34.0% and 15.3%, respectively (P=0.0001); CR rates were 21.1% and 10.5% (2-sided P=0.0106). Median EFS was 2.8 months and 0.7 months in the gilteritinib and SC arms, respectively (HR 0.793, P=0.0830). Common adverse events (AEs) in all randomized patients were febrile neutropenia (43.7%), anemia (43.4%), and pyrexia (38.6%). Common grade ≥3 AEs related to gilteritinib were anemia (19.5%), febrile neutropenia (15.4%), thrombocytopenia (12.2%), and decreased platelet count (12.2%). Adjusted for exposure duration, serious treatment-emergent AEs per patient year were less common with gilteritinib (7.1%) than SC (9.2%).

Conclusion
In patients with R/R FLT3mut+ AML, the potent, selective FLT3 inhibitor gilteritinib resulted in significantly longer overall survival and higher response rates compared with chemotherapy and had a favorable safety profile. These results change the treatment paradigm for salvage therapy of R/R FLT3mut+ AML and establish gilteritinib as the new standard of care.

Session topic: 4. Acute myeloid leukemia - Clinical

Keyword(s): Acute myeloid leukemia, Flt3 inhibitor, Salvage chemotherapy

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