FLT3 inhibitors in AML: Current clinical landscape and key insights from trials

The AML Hub was pleased to speak with Mark J. Levis, Johns Hopkins University, Baltimore, US. We asked, What is the current clinical landscape of FLT3 inhibitors in the treatment of AML, and what insights have been gained from trials so far?

Levis provides an overview of the key FLT3 inhibitors in clinical development for the treatment of FLT3-mutated (FLT3m) AML and discusses ongoing questions, including how to select the most appropriate FLT3 inhibitor for different patient populations and how best to incorporate them into standard treatment regimens. He highlights the value of measurable residual disease (MRD) in monitoring disease status as an important insight from clinical trials.

Key points

• FLT3 inhibitors are recommended as part of the treatment regimen for patients with FLT3m AML, based on improved clinical outcomes demonstrated in several clinical trials.^1–5
• Four FLT3 inhibitors are currently approved across the world – quizartinib, gilteritinib, midostaurin, and sorafenib – and an ongoing challenge in clinical practice is determining which FLT3 inhibitor might be most appropriate for specific treatment settings, while considering that their availability and regulatory status vary between regions.
  • For example, quizartinib is approved for the treatment of newly diagnosed (ND) FLT3-internal tandem duplication (FLT3-ITD) AML and as maintenance therapy; gilteritinib is approved for relapsed/refractory (R/R) FLT3m AML; and midostaurin is approved for ND FLT3m AML and as maintenance therapy in FLT3m AML.^6–11
• Incorporating FLT3 inhibitors into less intensive regimens, such as azacitidine + venetoclax, for patients who are ineligible for intensive chemotherapy, remains a key unmet need.
• The optimal integration of FLT3 inhibitors into treatment strategies, including intensive induction regimens and allo-HSCT, has also not yet been fully established.
• Clinical trials increasingly support the use of MRD assessment to monitor remission status and guide treatment decisions involving FLT3 inhibitors.
• While substantial progress has been made in establishing FLT3 inhibitors as a key element of care for FLT3m AML, further investigation is required to define optimal treatment strategies for different patient populations.

This educational resource is independently supported by Daiichi Sankyo. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence.