Ep. 3: FLT3-Mutated AML: Maintenance Therapy, Triplet Regimens, and Relapse Management

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, spoke with 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, about evolving maintenance strategies and treatment sequencing for FLT3-mutated AML. This segment focused on the role of MRD testing after allogeneic stem cell transplantation, emerging lower-intensity triplet regimens, and therapeutic approaches for relapsed or refractory disease.

Dr. Borate noted that highly sensitive FLT3 MRD assays, such as those used in the MORPHO trial, have become valuable tools for identifying patients most likely to benefit from posttransplant maintenance. However, the panel acknowledged that these assays are not universally available and often need to be sent out for specialized testing. Dr. Short explained that when highly sensitive MRD testing is unavailable or results remain uncertain, clinicians may favor FLT3 inhibitor maintenance to avoid undertreatment. 

The discussion shifted to patients who are not candidates for intensive induction chemotherapy. Dr. Daver reviewed emerging data evaluating triplet regimens combining hypomethylating agents, venetoclax, and FLT3 inhibitors. Importantly, the panel cautioned that careful dose optimization is essential to minimize prolonged myelosuppression. Clinical trials have demonstrated that abbreviated treatment schedules, rather than full-duration therapy for each agent, improve tolerability while maintaining efficacy. Although these regimens continue to be investigated, the experts encouraged referral to experienced leukemia centers or clinical trials whenever possible.

The panel addressed treatment considerations for relapsed FLT3-mutated AML. Dr. Short emphasized that single-agent gilteritinib remains the standard approach for patients who have not received it before, often serving as a bridge to allogeneic stem cell transplantation. Combination strategies incorporating venetoclax may be appropriate for selected transplant-eligible patients but require close monitoring because of increased hematologic toxicity. For patients who relapse after prior FLT3 inhibitor exposure, treatment decisions become much more challenging, reinforcing the importance of repeat molecular testing to confirm persistent FLT3 mutations and identify alternative treatment options.