Dr Stein on the FDA Approval of Revumenib for R/R, NPM1-Mutant AML

“Having a targeted therapy that goes after this mutation opens therapeutic options for patients who didn’t have those options before, with an oral medication that is generally well tolerated.”

Eytan M. Stein, MD, chief of the Leukemia Service and director of the Program for Drug Development in Leukemia in the Division of Hematologic Malignancies at Memorial Sloan Kettering Cancer Center, discussed the significance of the FDA approval of revumenib (Revuforj) for patients with relapsed/refractory, NPM1-mutant acute myeloid leukemia (AML).

On October 24, 2025, the FDA approved revumenib for the treatment of adult and pediatric patients 1 year of age or older with relapsed/refractory AML harboring a susceptible NPM1 mutation who have no satisfactory alternative treatment options. This regulatory decision was backed by data from the phase 1/2 AUGMENT-101 trial (NCT04065399).

The approval of revumenib, a menin inhibitor, for patients with NPM1-mutant relapsed or refractory AML represents a major breakthrough in addressing a critical unmet clinical need, Stein began. This drug, which is administered orally, is generally well tolerated, he noted. Previously, in November 2024, revumenib was FDA approved for the treatment of a different cohort of patients with relapsed or refractory AML—those with KMT2A translocations. The most recent approval’s focus on the NPM1 mutation is significant because this subtype of AML previously lacked specific, targeted therapies, according to Stein.

Although NPM1-mutant AML is frequently curable when treated with standard therapy in the frontline setting, patients who relapse on or are refractory to frontline treatment or subsequent therapies face inferior outcomes, Stein explained. The prognosis for this population is comparable with that of other cases of relapsed or refractory AML, where the median overall survival tends to be less than 1 year, he reported.

Revumenib is a targeted therapy designed to target KMT2A-menin activity, which the mutated NPM1 protein interacts with. The introduction of this agent into the treatment paradigm provides an effective therapy for patients who previously had extremely limited choices, Stein emphasized. This development provides a necessary specialized approach for patients who experience relapse or resistance to standard treatments, offering a medication that targets the underlying disease mechanism of NPM1-mutated AML, he concluded.