Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Novel combination therapies in treatment of newly diagnosed AML
Hematology Disease Topics & Pathways:
Adult, Diseases, Therapies, Combinations, Study Population, Clinically relevant, Myeloid Malignancies
Methods: This study is enrolling patients with ND FLT3mut+ (ITD or TKD [D835/I836]) AML who are (a) ≥65 years old and deemed ineligible for intensive induction chemotherapy by the investigator; or (b) ≥18–64 years old with specific comorbidities causing ineligibility for intensive induction chemotherapy. The study was initiated with a Safety Cohort in which patients received oral gilteritinib 80 mg/d as the initial dose on Days 1–28 (or 120 mg/d as the next dose level) plus AZA 75 mg/m2/d on Days 1–7. This was followed by a Randomization Cohort where ~250 patients are planned to be randomized 2:1 to receive oral gilteritinib on Days 1–28 plus AZA 75 mg/m2/d SC/IV on Days 1–7 (Arm AC) or AZA alone, administered in 28-day cycles (Arm C) until lack of efficacy, unacceptable toxicity, or a discontinuation event occurs. An earlier protocol version included a gilteritinib-alone treatment arm (Arm A) that was removed. The primary endpoint is overall survival (OS). Secondary endpoints include event-free survival (EFS; key secondary endpoint), best response, remission rates (complete remission [CR], CR with incomplete hematologic recovery [CRi], CR with partial hematologic remission [CRp], composite CR [CRc; sum of CR, CRi, and CRp]) and duration, transfusion conversion and maintenance rates, leukemia-free survival, patient-reported fatigue, and safety and tolerability. One interim and one final analysis are planned when ~70 and 140 deaths are observed, respectively. OS and EFS will be analyzed using the stratified log-rank test, with strata of age (≥75 vs <75 years), cytogenetic risk (favorable or intermediate vs unfavorable or secondary AML), and FLT3 mutation status (FLT3 TKD vs FLT3 ITD low allelic ratio [<0.5] vs FLT3 ITD high allelic ratio [≥0.5]).
Results Characteristics of all patients enrolled in the Safety and Randomization Cohorts as of 29 June 2020 are presented in Table 1. In the Safety Cohort, 15 patients were enrolled. Fourteen patients have died, and 1 patient continued on treatment (Figure). The median (range) treatment duration was 6 (<1–34) cycles; 40% (n=6/15) received >12 cycles of treatment. Overall, a CRc of 67% (n=10/15) was observed (Figure). Based on these data, a gilteritinib dose of 120 mg daily plus AZA was adopted for the Randomization Cohort. As of 29 June 2020, 136 patients had been randomized with 114 in Arm AC or C and 22 in Arm A (now closed). Median (range) treatment duration was 4 (<1–31) cycles, with 40% (n=54/136) having received ≥6 treatment cycles. A total of 83 patients (61%) in the Randomization Cohort died.
Conclusions: The study is ongoing, and no new safety signals associated with gilteritinib 120 mg daily plus AZA have been observed thus far in the study. Mature remission data from the Safety Cohort of gilteritinib 80-120 mg plus AZA shows a CRc rate of 67%. Patients with ND FLT3mut+ AML considered unfit for intensive chemotherapy continue to be randomized 2:1 to receive gilteritinib 120 mg/d plus AZA vs AZA alone for upfront treatment.
Disclosures: Wang: Abbvie: Consultancy; Pfizer: Speakers Bureau; Genentech: Consultancy; Bristol Meyers Squibb (Celgene): Consultancy; Macrogenics: Consultancy; Astellas: Consultancy; Stemline: Speakers Bureau; PTC Therapeutics: Consultancy; Jazz Pharmaceuticals: Consultancy. Montesinos: Celgene, Pfizer, Abbvie: Consultancy; Pfizer, Abbvie, Daiichi Sankyo: Research Funding; Astellas, Novartis, Janssen: Speakers Bureau. Lee: Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Heuser: Pfizer: Consultancy, Honoraria, Research Funding; Stemline Therapeutics: Consultancy; Bayer: Consultancy, Research Funding; Roche: Research Funding; Karyopharm: Research Funding; Amgen: Research Funding; PriME Oncology: Honoraria; Astellas: Research Funding; Abbvie: Consultancy; Novartis: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; BerGenBio ASA: Research Funding; Janssen: Consultancy. Naoe: Sysmex co.: Speakers Bureau; Astellas Pharma Inc.: Speakers Bureau; Eisai Co., Ltd.: Speakers Bureau; Bristol-Myers Squibb Company: Speakers Bureau; NIPPON SHINYAKU CO.,LTD.: Speakers Bureau. Liu: Astellas: Current Employment. Wu: Astellas: Current Employment. Philipose: Astellas: Current Employment. Rich: Astellas: Current Employment. Tiu: Astellas Pharma Global Development: Current Employment; Eli Lilly & Company: Current equity holder in publicly-traded company, Ended employment in the past 24 months.
OffLabel Disclosure: New Indication
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