Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy, with FLT3 mutations among the most common molecular abnormalities, significantly impacting patient prognosis. As our understanding of AML pathogenesis deepens, novel targeted therapies, including FLT3 inhibitors, have emerged, offering new hope for patients with FLT3-mutated AML. From January 17 to 19, 2025, the "CSCO Leukemia, Lymphoma, and Myeloma Expert Committee Working Meeting & 2025 CSCO Hematologic Oncology Conference" was held in Haikou, China. During the event, Hematology Frontier had the privilege of interviewing Dr. Hui Wei from the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences. He shared insights into the prevalence of FLT3 mutations in AML, recent advancements in targeted therapy, and future optimization strategies.

FLT3 Mutations in AML: Frequency and Clinical Impact

FLT3 is one of the most frequently mutated genes in AML, with significant implications for prognosis and treatment decisions. Dr. Hui Wei explained that FLT3 mutations occur in 30% to 40% of AML patients, with a prevalence of approximately 30% in younger patients and 20% in older patients. These mutations are associated with poor outcomes, particularly due to increased relapse rates among patients who achieve first complete remission (CR1). Additionally, in relapsed or refractory AML cases, FLT3 mutations contribute to reduced remission rates and lower long-term survival. Currently, hematopoietic stem cell transplantation remains the primary treatment recommendation for patients with FLT3-mutated AML.

Breakthroughs in Targeted Therapy for FLT3-Mutated AML

With advancements in precision medicine, FLT3 inhibitors have transformed the treatment landscape for AML, bringing significant progress in recent years. Dr. Hui Wei highlighted that, although broad-spectrum BCL-2 inhibitors have improved remission rates, their long-term survival benefits remain uncertain for FLT3-mutated AML. The most crucial development in this field has been the introduction of FLT3 inhibitors.

From first-generation to second-generation FLT3 inhibitors, agents such as gilteritinib and quizartinib have demonstrated remarkable efficacy, particularly in relapsed or refractory AML. In these patients, monotherapy with quizartinib or gilteritinib has shown superior remission rates compared to traditional combination chemotherapy. Furthermore, in frontline treatment, quizartinib combined with the standard “3+7” induction regimen, followed by consolidation chemotherapy and maintenance therapy, has significantly improved patient outcomes. As the use of FLT3 inhibitors expands, they are expected to alter the historically poor prognosis of FLT3-mutated AML, leading to increasingly favorable treatment results.

Challenges and Future Directions in FLT3-Mutated AML Therapy

Despite significant advances, challenges remain in the diagnosis and treatment of FLT3-mutated AML. According to Dr. Hui Wei, two primary issues persist. First, while multiple targeted therapies are available, treatment outcomes remain suboptimal, with long-term survival rates hovering around 50% to 60%. Second, current treatment strategies still rely on chemotherapy and transplantation combined with FLT3 inhibitors or other targeted agents, leading to considerable toxicity. A major challenge moving forward is to develop low-toxicity or even chemotherapy-free regimens.

Future research must focus on optimizing treatment strategies, particularly FLT3 inhibitor-based combination therapies. This includes refining the integration of FLT3 inhibitors with chemotherapy and exploring rational combinations with agents such as BCL-2 inhibitors and hypomethylating agents. The ultimate goal is to enhance efficacy while minimizing treatment-related toxicity, paving the way for more effective and well-tolerated therapeutic approaches for FLT3-mutated AML.

About the Expert

• Hui Wei Chief Physician, PhD Supervisor Director, Leukemia Diagnosis and Treatment Center Deputy Director, National Clinical Research Center for Hematologic Diseases Member, Hematology Branch of the Chinese Medical Association Vice Chair, Leukemia and Lymphoma Group Vice Chair, Hematologic Oncology Committee, Chinese Anti-Cancer Association Associate Editor, Hematological Oncology Specializes in basic and clinical research on leukemia