Menin inhibitors in AML: Bridging the gap between trial data and clinical practice

The AML Hub was pleased to speak with Emma Searle, The Christie NHS Foundation Trust, Manchester, UK. We asked for her thoughts on the topic “Menin inhibitors in AML: Bridging the gap between trial data and clinical practice.”

Searle provides an overview of key considerations for the use of menin inhibitors in the treatment of NPM1-mutated (NPM1m) or KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML) in clinical practice, and her thoughts on key areas of interest looking forward.

Key learnings 

• A number of menin inhibitors are being evaluated in clinical trials, both as monotherapies and in combination strategies, for the treatment of NPM1m or KMT2Ar AML. At present, the U.S. Food and Drug Administration (FDA) has approved revumenib as monotherapy for patients aged ≥1 year with KMT2Ar relapsed/refractory (R/R) acute leukemia.¹
• The development of menin inhibitors for AML treatment has so far yielded overall response rates (ORRs) of ~40–60%, and complete remission (CR) or CR with partial hematologic recovery rates of ~25–45%, when used as monotherapy.
• The potential for toxicity is a key consideration for the forthcoming integration of menin inhibitors into clinical practice.
  • Differentiation syndrome is an established class effect of menin inhibition that can develop promptly and result in poor outcomes. Strategies for managing differentiation syndrome include monitoring for inflammatory response, and holding menin inhibitor therapy to administer steroids, to control the inflammatory response.
  • Differences in toxicity profiles may impact treatment decisions and monitoring approach; QTc prolongation, for instance, has been observed with revumenib, but not with bleximenib or enzomenib.
• Key future areas of interest in the menin inhibitor landscape include investigation in different patient populations and at different stages of the patient journey, for instance:
  • Evaluation in the upfront setting and in patient populations other than those with NPM1m or KMT2Ar AML, such as those with NUP98 rearrangements.
  • Studies investigating menin inhibition at molecular relapse, as maintenance post-allogeneic hematopoietic stem cell transplantation (post allo-HSCT), and in combination strategies with both chemotherapy and non-intensive regimens, are ongoing.

This educational resource is independently supported by Johnson & Johnson. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.