OPEN-LABEL STUDY OF GILTERITINIB, GILTERITINIB VERSUS AZACITIDINE, OR AZACITIDINE
ALONE IN NEWLY DIAGNOSED FLT3-MUTATED AML PATIENTS INELIGIBLE FOR INTENSIVE
POSTER 13
CHEMOTHERAPY: RESULTS FROM THE SAFETY COHORT
Jordi Esteve1, Rik Schots2, Teresa Bernal Del Castillo3, Je-Hwan Lee4, Eunice S. Wang5, Shira Dinner6,
Mark D. Minden7, Olga Salamero8, Jorge Sierra9, Goichi Yoshimoto10, Kamel Laribi11, Janusz Halka12,
Pau Montesinos13, Shufang Liu14, Elizabeth Shima Rich14 and Erkut Bahceci14
(1)Hospital Clínic, Barcelona, Spain
(2)UZ-Brussel-VUB, Jette, Belgium
(3)Hospital Universitario Central de Asturias, Oviedo, Spain
(4)Asan Medical Center, Seoul, Korea, Republic of (South)
(5)Roswell Park Comprehensive Cancer Center, Buffalo, NY
(6)Robert H. Lurie Comprehensive Cancer Center, Chicago, IL
(7)Princess Margaret Hospital, Toronto, Canada
(8)Hospital Vall D´Hebron, Barcelona, Spain
(9)Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
(10)Kyushu University Hospital, Fukoka, Japan
(11)Centre Hospitalier Du Mans, Le Mans, France
(12)Warmian-Masurian Cancer Center of The Ministry of the Interior and Administration’s Hospital,
Warsaw, Poland
(13)Hospital Universitari i Politècnic La Fe, Valencia & CIBERONC, Instituto Carlos III, Madrid, Spain
(14)Astellas Pharma US, Inc., Northbrook, IL
Objective: The FLT3 inhibitor, gilteritinib, demonstrated efficacy with favorable tolerability in
patients with FLT3-mutated (FLT3mut+) relapsed/refractory AML. Gilteritinib plus azacitidine (AZA)
induced apoptosis and inhibited tumor growth. A trial (NCT02752035) investigating gilteritinib plus
AZA vs AZA alone in adults with newly diagnosed (ND) FLT3mut+ AML ineligible for intensive
chemotherapy was initiated; we present data from the Safety Cohort, which evaluated combination
therapy.
Methods: Patients in the Safety Cohort received 80- or 120-mg/day gilteritinib (Days 1-28) plus AZA
(75 mg/m2/day; Days 1-7). Safety/tolerability and antileukemic response were assessed.
Results: The Safety Cohort comprised 15 patients (median age, 76 years range: 65-86; n=9, 80-mg
gilteritinib; n=6, 120-mg gilteritinib); 14 were FLT3mut+. As of 25 June 2018, 56% (n=8/15) of patients
had been treated for >6 months; nine discontinued, and six remained on treatment. A patient who
received 80-mg gilteritinib plus AZA had a dose-limiting toxicity (DLT; tumor lysis syndrome); no DLTs
occurred in the 120-mg gilteritinib plus AZA cohort. All 15 patients had ≥1 adverse event (AE); 12
(80%) experienced treatment-related AEs. Common AEs were anemia (n=7), febrile neutropenia and
nausea (n=6 each), increased ALT/AST, constipation, diarrhea, neutropenia, thrombocytopenia and
pyrexia (n=5 each), and decreased appetite, fatigue, increased blood creatinine, and hypocalcemia
(n=4 each). Common grade ≥3 AEs were febrile neutropenia (n=6), anemia and neutropenia (n=5
each), and thrombocytopenia (n=4). Serious AEs in >2 patients were febrile neutropenia (n=5), and
anemia and pyrexia (n=3 each). Eight patients had fatal AEs, but none were treatment-related; three
occurred early in treatment (septic shock on Day 2, respiratory failure on Day 6, cerebral hemorrhage
in the setting of acute kidney injury and uremia on Day 17). Of 13 patients with postbaseline
laboratory data, none had clinically significant AST/ALT, or total bilirubin values or maximum
postbaseline QTcF interval >500 msec.
SCIENTIFIC
PROGRAMME
RARE SUBSETS OF
ACUTE LEUKAEMIA
TRACKING LEUKAEMIC
STEM CELLS (LSCs)
ROUTINE DIAGNOSIS
GENE EXPRESSION
AND MUTATIONAL
PROFILING
DEBATE 1 – ALL
PATIENTS WITH
INTERMEDIATE-RISK
AML MUST BE
TRANSPLANTED
INTERACTIVE
CASES 1 – MUTATION-BASED
THERAPY
OFF-LABEL
ROUNDTABLE –
SHOULD WE REALLY
USE NEW TARGETED
INHIBITORS AS SINGLE
AGENTS ?
ADDITION OF A 3RD
AGENT TO FRONTLINE
7+3
ROUNDTABLE –
CURATIVE OPTIONS
FOR OLDER AML
INTERACTIVE CASES 2
DEBATE 2 - BEST
TREATMENT FOR
NPM1-MUTATED AML IN
THE NEXT FUTURE ?
ALLOGENEIC
HAEMATOPOIETIC
STEM CELL
TRANSPLANTATION
(HSCT)
IMMUNOTHERAPY FOR
ACUTE LEUKAEMIA
DEBATE 3 - T-ALL:
WHERE ARE WE GOING
NOW?
SELECTED ABSTRACTS
AND CLINICAL
CASES FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FOR A POSTER
PRESENTATION
DISCLOSURES