Ep. 2: FLT3 Inhibitors Continue to Expand Treatment Opportunities in Acute Myeloid Leukemia

During a recent Clinical Insights discussion, Oncology Brothers podcast cohosts Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, and Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, were joined by Uma Borate, MBBS, of The Ohio State University, and Naval Daver, MD, and Nicholas Short, MD, both of The University of Texas MD Anderson Cancer Center, to discuss FLT3 inhibitors’ evolving role in AML. In this segment, the panel reviewed pivotal clinical trials supporting current approvals of FLT3-targeted therapies, best practices for molecular testing, and emerging strategies for incorporating MRD into treatment decisions. 

Dr. Short reviewed the landmark studies that established FLT3 inhibitors as standard treatment options in AML. The RATIFY trial demonstrated an overall survival (OS) benefit with the addition of midostaurin to intensive induction and consolidation chemotherapy in younger adults with FLT3-mutated AML, leading to its approval in the frontline setting. More recently, the QuANTUM-First trial showed improved survival with quizartinib combined with intensive chemotherapy in patients with FLT3–internal tandem duplication (ITD) AML, expanding treatment options for fit patients up to age 75. In the relapsed or refractory setting, the ADMIRAL trial established gilteritinib as the standard of care after demonstrating superior response rates and OS compared with salvage chemotherapy. 

Although FLT3 inhibitor monotherapy provides meaningful clinical benefit, Dr. Short emphasized that these agents should generally serve as a bridge to allogeneic stem cell transplantation rather than as curative therapy alone.

The discussion also addressed how clinicians interpret FLT3 mutation burden and incorporate repeat molecular testing into routine practice. Dr. Borate explained that although higher FLT3 allelic burden was once considered an important prognostic factor, current treatment decisions are driven more by the presence of a FLT3 mutation itself, co-occurring genomic alterations, patient fitness, and overall treatment strategy. Because FLT3 mutations may disappear after treatment or emerge during disease progression, reassessing mutation status ensures that patients remain eligible for the most appropriate targeted therapies. The experts noted that acquisition or loss of FLT3 mutations occurs often enough that repeat testing has become a standard part of relapse evaluation.

The panel concluded by examining the expanding role of FLT3 inhibitors beyond induction therapy. Dr. Daver reviewed data supporting maintenance therapy following induction and consolidation, noting that QuANTUM-First demonstrated prolonged remission among patients who received quizartinib maintenance instead of proceeding to transplant. He also discussed evolving evidence supporting posttransplant maintenance, particularly findings from the MORPHO trial evaluating gilteritinib. Although the study narrowly missed its primary end point, patients with detectable FLT3 MRD before or after transplant experienced improved relapse-free survival with maintenance gilteritinib.