Gilteritinib, a selective FLT3 inhibitor, is approved for the treatment of relapsed/refractory (R/R) FLT3-mutated AML and has demonstrated survival benefits in global trials. However, long-term data in predominantly Asian populations have remained limited. 

Gilteritinib was administered at a daily dose of 120 mg, while salvage chemotherapy included established regimens such as low-dose cytarabine or high-dose cytarabine-based combinations. The trial aimed to assess long-term survival outcomes, remission rates, transplant rates, and overall tolerability in this regional patient cohort.

A total of 276 patients were randomized equally between the gilteritinib and salvage chemotherapy arms, with 88% being Asian. With a median follow-up exceeding 34 months, gilteritinib significantly improved median overall survival (10.3 vs. 5.4 months) and event-free survival (2.1 vs. 0.6 months) compared to salvage chemotherapy. Response outcomes favored gilteritinib, with higher complete remission (CR: 20.4% vs. 11.5%), composite CR (53.3% vs. 22.3%), and overall response (67.9% vs. 27.3%) rates. Time to remission was longer with gilteritinib, but more durable. More patients in the gilteritinib arm underwent hematopoietic stem cell transplantation (HSCT), and most who resumed gilteritinib post-HSCT tolerated it well. Transfusion independence was also improved in this group. No new safety concerns emerged, supporting gilteritinib's favorable risk-benefit profile in this population.

KOL insights

“Over the years, several FLT3 inhibitors have shown promising results in clinical trials. At present, three FLT3 inhibitors—midostaurin, gilteritinib, and quizartinib—are approved for the treatment of ND and R/R patients across different treatment phases, including induction, consolidation, and maintenance. More research is needed to explore various combination strategies, identify strategies to overcome resistance, and further explore the benefits of FLT3 inhibitors in maintenance therapy.”– Expert Opinion

Conclusion

AML with FLT3 mutations is a common, complex, and high-risk condition that demands a deep understanding of cellular signaling pathways, the tumor microenvironment, and immune system dynamics. While FLT3 inhibitors have become a key component of therapy for these patients, ongoing advancements in medical practice highlight the need to overcome several remaining challenges.

For newly diagnosed patients with FLT3-mutated AML, the standard approach typically includes 3+7 induction chemotherapy combined with midostaurin. To reduce the likelihood of relapse, allogeneic hematopoietic cell transplantation (HCT) is often recommended as post-remission therapy. Although the role of FLT3 inhibitors in post-transplant maintenance is not yet fully defined, emerging expert consensus supports their potential to lower relapse risk. Additionally, gilteritinib has demonstrated superiority over salvage chemotherapy in patients with relapsed or refractory FLT3-mutated AML. Ongoing clinical trials aim to expand therapeutic options by tailoring treatment to disease stage and individual patient risk profiles.