The following is a summary of “Understanding Mechanisms of Resistance to FLT3 inhibitors in Adult FLT3-mutated Acute Myeloid Leukemia (AML) to guide treatment strategy,” published in the June 2024 issue of Oncology/Hematology by Ruglioni et al.

The presence of FLT3 mutations, particularly FLT3-ITD (internal tandem duplications) and FLT3-TKD (tyrosine kinase domain) variants, significantly influences the clinical prognosis of patients with Acute Myeloid Leukemia (AML). Over recent years, the introduction of new FLT3 inhibitors has shown promising results in improving overall survival and treatment response rates. Despite these advancements, the development of both primary and secondary mechanisms of resistance poses a formidable challenge to the effectiveness of these therapies. Therefore, gaining a deeper understanding of these resistance mechanisms is crucial for devising novel therapeutic approaches aimed at overcoming these barriers and enhancing patient outcomes.

Recent studies have explored various strategies to address resistance, including the use of next-generation FLT3 inhibitors and combination therapies with other targeted agents. These approaches aim not only to circumvent resistance mechanisms but also to optimize treatment outcomes in FLT3-mutated AML. This review critically examines the molecular alterations that underlie resistance mechanisms specific to FLT3-mutated AML, shedding light on how these insights can inform clinical decision-making through molecular monitoring. By elucidating these mechanisms, researchers and clinicians can better tailor treatment strategies, potentially improving response rates and prolonging survival in this challenging subset of patients with AML.

Source: sciencedirect.com/science/article/pii/S1040842824001677