Treatment of older adults with newly diagnosed FLT3-mutated AML: focus on lower-intensity triplet regimens.

INTRODUCTION: Treatment options for older adults with FLT3-mutated AML who are unfit for intensive chemotherapy have evolved substantially. The combination of hypomethylating agent (HMA) and venetoclax is the current standard-of-care regimen for these patients, though outcomes remain suboptimal, particularly in FLT3-ITD mutated AML. More recently, encouraging data have emerged supporting the safety and efficacy of frontline HMA + venetoclax + FLT3 inhibitor 'triplet' regimens. AREAS COVERED: We summarize the available evidence for different frontline treatment approaches in older adults with FLT3-mutated AML. We also discuss key practical considerations for the use of triplet regimens and provide recommendations to optimize drug doses and durations and improve tolerability. Relevant literature search was carried out using PubMed/MEDLINE databases through June 2026. EXPERT OPINION: The HMA + venetoclax + FLT3 inhibitor triplet regimens, when administered with appropriate dose optimization and supportive care, can be delivered safely, with very high response rates and improved long-term survival in older adults with FLT3-mutated AML, positioning them as a potential new standard-of-care option. However, randomized controlled trial data are still awaited, and their safe administration requires close monitoring, robust supportive care and expertise that is most readily available at specialized academic centers.