UPDATED RESULTS FROM A PHASE 1 STUDY OF GILTERITINIB IN COMBINATION WITH INDUCTION AND CONSOLIDATION CHEMOTHERAPY IN PATIENTS WITH NEWLY DIAGNOSED AML
Author(s): ,
Keith Pratz
Affiliations:
Sidney Kimmel Comprehensive Cancer Center,Johns Hopkins University,Baltimore,United States
,
Mohamad Cherry
Affiliations:
Stephenson Cancer Center,University of Oklahoma,Oklahoma City,United States
,
Jessica Altman
Affiliations:
Robert H. Lurie Comprehensive Cancer Center,Northwestern University Feinberg School of Medicine,Chicago,United States
,
Brenda Cooper
Affiliations:
University Hospitals, Cleveland Medical Center,Cleveland,United States
,
Jose Carlos Cruz
Affiliations:
Methodist Physician Practices,San Antonio,United States
,
Joseph Jurcic
Affiliations:
Columbia University Medical Center,New York,United States
,
Mark Levis
Affiliations:
Sidney Kimmel Comprehensive Cancer Center,Johns Hopkins University,Baltimore,United States
,
Tara Lin
Affiliations:
University of Kansas Medical Center,Kansas City,United States
,
Alexander Perl
Affiliations:
Abramson Comprehensive Cancer Center,University of Pennsylvania,Philadelphia,United States
,
Nikolai Podoltsev
Affiliations:
Yale School of Medicine,New Haven,United States
,
Gary Schiller
Affiliations:
David Geffen School of Medicine at UCLA,Los Angeles,United States
,
Chaofeng Liu
Affiliations:
Astellas Pharma Global Development,Northbrook,United States
Erkut Bahceci
Affiliations:
Astellas Pharma Global Development,Northbrook,United States
EHA Library. Perl A. Jun 15, 2019; 266653; PS1036
Alexander Perl
Alexander Perl
Contributions
Abstract

Abstract: PS1036

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background
As a single agent, the FLT3 inhibitor, gilteritinib, elicited antileukemic responses in patients with FLT3-mutated (FLT3mut+) relapsed/refractory AML. 

Aims
We evaluated once-daily oral gilteritinib combined with front-line chemotherapy in patients with newly diagnosed (ND) AML.

Methods
This ongoing open-label, phase 1 study (NCT02236013) assesses the safety/tolerability and antitumor effects of gilteritinib combined with 7+3 induction and high-dose cytarabine consolidation chemotherapy, and as single-agent maintenance therapy in adults with ND AML. During dose escalation, successive cohorts of 3–6 patients received 40, 80, 120, or 200 mg/day of gilteritinib (Days 4–17 [Schedule 1]) and ≤2 cycles of induction (cytarabine 100 mg/m2/day, Days 1–7, idarubicin 12 mg/m2/day, Days 1–3). During dose expansion, patients received the recommended expansion dose of gilteritinib (Schedule 1) combined with 7+3 idarubicin induction. Two additional cohorts received gilteritinib on Days 8–21 (Schedule 2) with idarubicin (n=6; 12 mg/m2/day) or daunorubicin (n=5; 90 mg/m2/day) on Days 1–3. During consolidation, patients received cytarabine (1.5 g/m2 every 12 hours, Days 1, 3, and 5) and gilteritinib (Days 1–14) at the induction dose for ≤3 cycles. After consolidation or transplantation, patients received gilteritinib (40, 80, or 120 mg/day) maintenance therapy.

Results
Of 68 patients enrolled as of October 8, 2018 (safety analysis set, n=66), most were male (63.6%; median age, 59.5 years [range, 23–77]); 36 (54.5%) were FLT3mut+ (FLT3-ITD, n=25; FLT3-TKD D835, n=7; FLT3-ITD and -TKD D835, n=1; other FLT3 mutation, n=3). Two patients in the 200 mg/day cohort experienced dose-limiting toxicities (neutropenia, neutropenic enterocolitis). The maximum tolerated dose and the recommended expansion dose were established at 120 mg/day. Common grade ≥3 adverse events (AEs) were febrile neutropenia (63.6%), thrombocytopenia (19.7%), neutropenia (19.7%), decreased white blood cell count (19.7%), decreased platelet count (19.7%), and decreased neutrophil count (16.7%). Serious drug-related AEs in >1 patient were febrile neutropenia (n=11), sepsis (n=4), small intestinal obstruction (n=2), and decreased ejection fraction (n=2). End-of-treatment investigator-reported composite complete remission (CRc) rate for evaluable FLT3mut+ patients receiving gilteritinib on Schedule 1 (n=22) was 100%. The CRc rate in FLT3mut+ patients receiving Schedule 2 induction with either idarubicin or daunorubicin (n=11) was 81.8% (Table). Median overall survival has not been reached. 

Conclusion
Gilteritinib can be safely combined with chemotherapy and given as maintenance therapy in patients with ND AML. High response rates were observed in FLT3mut+ patients regardless of anthracycline type or gilteritinib administration schedule.

Session topic: 4. Acute myeloid leukemia - Clinical

Keyword(s): Acute myeloid leukemia, Chemotherapy, Flt3 inhibitor

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies