Adding giritinib to induction and consolidation chemotherapy and maintenance therapy in patients with newly diagnosed AML

In a reported Phase Ib trial (2215-CL-0103), researchers incorporating the FLT3 inhibitor Gilteritinib into intensive induction and consolidation chemotherapy and using it as single-agent maintenance therapy was associated with activity in patients with newly diagnosed FLT3-mutated acute myeloid leukemia (AML). The study consisted of four parts: a dose-escalation, dose-expansion, study of alternating anthracycline andgiritinib regimens, and a consolidation phase of continuous geritinib.

After dose escalation, once-daily 120 mg of geritinib was selected for further study. A total of 58 patients were evaluable for response to this dose, including 36 patients with FLT3 mutations and 22 patients with wild-type FLT3. Composite complete responses (complete response, complete response with incomplete platelet recovery, and complete response with incomplete count recovery) were observed in 32 (89%) patients with FLT3 mutations (including 50% complete responses) and 11 (50%) patients with wild-type FLT3. Among patients treated with 120 mg of giritinib once daily, median overall survival was 46.1 months for patients with FLT3 mutations and 38.7 months for patients with wild-type FLT3.

Giritinib was well tolerated, although the median time to count recovery during induction was approximately 40 days. Longer count recovery times were associated with higher gilitinib trough levels; higher trough levels were associated with azole use. The recommended regimen was determined to be giritinib 120 mg once daily, induction with idarubicin or daunorubicin from day 4 to day 17 or day 8 to day 21 of 7+3 induction, and continuous consolidation with high-dose cytarabine starting from day 1.

These results demonstrate the safety and tolerability of giritinib when incorporated into induction and consolidation chemotherapy regimens, and as single-agent maintenance therapy in patients with newly diagnosed FLT3-mutant AML. The data provide an important framework for designing randomized trials comparing geritinib with other FLT3 inhibitors.