In a phase Ib trial (2215-CL-0103) reported in the Journal of Clinical Oncology, Keith W. Pratz, MD, and colleagues found that incorporation of the FLT3 inhibitor gilteritinib into intensive induction and consolidation chemotherapy and its use as single-agent maintenance therapy were associated with activity in newly diagnosed patients with FLT3-mutated acute myeloid leukemia (AML).
In the U.S. multicenter study, 80 patients with non–favorable-risk disease were enrolled between January 2015 and December 2019 irrespective of FLT3 mutation status. The study consisted of four parts: dose escalation, dose expansion, investigation of alternate anthracycline and gilteritinib schedule, and continuous gilteritinib during consolidation.
Keith W. Pratz, MD
After dose escalation, gilteritinib at 120 mg once daily was selected for further study. A total of 58 patients were evaluable for response at this dose, including 36 with a FLT3 mutation and 22 with wild-type FLT3.
Composite complete response (complete response, complete response with incomplete platelet recovery, and complete response with incomplete count recovery) was observed in 32 patients (89%) with a FLT3 mutation (including complete response in 50%) and in 11 patients (50%) with wild-type FLT3. Among patients treated with gilteritinib at 120 mg once daily, median overall survival was 46.1 months among those with a FLT3 mutation and 38.7 months among those with wild-type FLT3.
Gilteritinib was well-tolerated, although median time to count recovery during induction was approximately 40 days. Longer time to count recovery was associated with higher trough levels of gilteritinib; higher trough levels were associated with the use of azoles.
The recommended regimen was identified as gilteritinib at 120 mg once daily from days 4 to 17 or 8 to 21 of a 7 + 3 induction with either idarubicin or daunorubicin, and from day 1 continuously with high-dose cytarabine consolidation.
Maintenance therapy with gilteritinib was also well-tolerated.
The investigators concluded, “These results demonstrated the safety and tolerability of gilteritinib incorporated into an induction and consolidation chemotherapy regimen, and as single-agent maintenance therapy for patients with newly diagnosed FLT3-mutant AML. The data herein provide an important framework for the design of randomized trials comparing gilteritinib with other FLT3 inhibitors.”
Mark J. Levis, MD, PhD, of the Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Astellas Pharma Global Development, Inc. For full disclosures of the study authors, visit ascopubs.org.