1. In this phase 3 trial, patients with relapsed or refractory acute myeloid leukemia who received gilteritinib had a longer median overall survival and a higher likelihood of complete remission versus chemotherapy. After factoring in therapy duration, serious adverse events also occurred less frequently in the gilteritinib group.
2. Despite these statistically significant improvements, long-term survival remained poor, indicating the need for further research into the timing and toxicity of intervention.
Evidence Rating Level: 1 (Excellent)
Study Rundown: FMS-like tyrosine kinase 3 (FLT3) is involved in the proliferation and differentiation of hematopoietic stem cells. When constitutively activated through mutation as in roughly 30% of patients with acute myeloid leukemia (AML), the enzyme sparks uncontrolled growth and adversely affects survival. Given the ineffectiveness of salvage chemotherapy as a second-line treatment for AML that is refractory to standard chemotherapy, FLT3 inhibitors have been a welcome addition to the arsenal of treatment options. However, issues have arisen with their selectivity and single-agent potency, stressing the continued need for a powerful molecule that demonstrates strong activity against both mutation subtypes (ITD and TKD) yet spares other essential kinases. This randomized study aimed to confirm the safety and efficacy of one such candidate, gilteritinib, in the treatment of relapsed or refractory FLT3-mutated AML. Patients treated with gilteritinib experienced both a longer median overall survival and a higher likelihood of complete remission with full or partial hematologic recovery compared to those who received salvage chemotherapy. The exposure-adjusted rate of adverse events of grade 3 or higher was also significantly lower in the gilteritinib group, with some of the most common events in both groups being febrile neutropenia, anemia, and thrombocytopenia. However, long-term survival rates remained poor in both groups. These promising findings beg further research into the timing of FLT3 intervention as well as its role in the grand scheme of potential treatments.