Menin Inhibitor Developments Move Acute Myeloid Leukemia Landscape Forward


Treatment with revumenib appeared to demonstrate efficacy among patients with KMT2A-rearranged acute leukemia in the phase 2 AUGMENT-101 study.

In a conversation with CancerNetwork® at the 2024 European Hematology Association (EHA) Congress, Eunice S. Wang, MD, highlighted findings related to the use of novel menin inhibitors as a development of interest in the acute myeloid leukemia (AML) space.

Specifically, Wang, chief of the Leukemia Service of the Department of Medicine at Roswell Park Comprehensive Cancer Center in Buffalo, New York, discussed data on revumenib as a treatment for those with KMT2A-rearranged disease as part of the phase 2 AUGMENT-101 study (NCT04065399). Findings showed that the inhibitor elicited a complete response (CR) and CR with hematologic recovery (CRh) rate of 23% (95% CI, 12.7%-35.8%) among 57 evaluable patients.1 According to Wang, these data may support the application seeking FDA approval for revumenib in this patient population.

The FDA granted priority review to revumenib in KMT2A-rearranged acute leukemia in March 2024.2 The agency set a Prescription Drug User Fee Act date of September 26, 2024 for the agent.


There’s a great deal of interest at this EHA for a novel class of agents called menin inhibitors. These are a potentially new category of agents that target specific subsets of AML that we have not been able to specifically inhibit in the past, and those are patients that have acute leukemias, AML, as well as ALL characterized by a KMT2A or MLL rearrangement, as well as up to one-third of [patients with] AML who have mutations in nucleophosmin 1, or NPM1.

Perhaps the most advanced [menin inhibitor] is the drug revumenib, which is being developed by Syndax. They presented updated results of a phase 2 study [NCT04065399] where they looked at 57 patients with KMT2A-rearranged acute leukemias and demonstrated the safety and the efficacy of their compound across this entire subset. They had overall response rates of 50% to 60%, and they had CR and CRh rates of 23% with manageable differentiation syndrome.1 There was still some QTc prolongation. This drug is going up for FDA approval later in September 2024, and these data were being presented to substantiate their application for that.

We also saw several newer inhibitors out there, [including] one from [Johnson & Johnson], where they’re doing monotherapy as well as combination [therapy]. We saw the results of revumenib combined with venetoclax [Venclexta]/azacitidine in the Beat AML trial [NCT03013998] with response rates of 100% in a very small number of patients, so this class of agents, I believe, is moving forward.3


  1. Aldoss I, Issa GC, Thirman M, et al. Revumenib monotherapy in patients with relapsed/refractory KMT2AR acute leukemia: topline efficacy and safety results from the pivotal AUGMENT-101 phase 2 study. Presented at the 2024 European Hematology Association (EHA) Congress; June 13-16, 2024; Madrid, Spain. Abstract S131.
  2. Syndax announces FDA priority review of NDA for revumenib for the treatment of relapsed/refractory KMT2Ar acute leukemia. News release. Syndax Pharmaceuticals Inc. March 26, 2024. Accessed June 25, 2024.
  3. Zeidner J, Lin TL, Welkie R, et al. Phase 1b study of azacitidine, venetoclax, and revumenib in newly diagnosed older adults with NPM1 mutated or KMT2A rearranged AML: interim results of dose escalation from the BEATAML Consortium. Presented at the 2024 European Hematology Association (EHA) Congress; June 13-16, 2024; Madrid, Spain. Abstract S134.
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