The FDA approved revumenib (Revuforj, Syndax Pharmaceuticals) for relapsed or refractory acute myeloid leukemia (R/R AML) with a susceptible nucleophosmin 1 (NPM1) mutation in adult and pediatric patients 1 year or older who have no satisfactory alternative treatment options.

It’s the second indication for the oral menin inhibitor after its initial approval in November 2024 for R/R acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation in adults and children.

Syndax noted in a press release that revumenib is now the first and only approved drug for both NPM1-muted R/R AML and KMT2A-translocated R/R acute leukemia.

Several other menin inhibitors are in development with activity in KMT2A translocations and/or NPM1-mutated disease.

Menin is a regulatory protein that normally helps blood cells differentiate; the genetic aberrations derail its normal activity, driving unchecked growth of immature cells. Menin inhibitors block the abnormal activity, helping restore normal differentiation and curb leukemic proliferation.

Approval of revumenib’s new indication was based on 84 NPM1-mutated patients in the single arm AUGMENT-101 trial. The mutation was confirmed by next generation sequencing or polymerase chain reaction.

The rate of complete remission or complete remission with partial hematologic recovery was 23.1%, with a median duration of 4.7 months.

Of the 46 patients dependent on red blood cell and/or platelet transfusions at baseline, eight (17%) became independent of both during any 56-day post-baseline period.

Syndax noted that revumenib has been added to National Comprehensive Cancer Network treatment guidelines for both R/R NPM1-mutated AML as well as KMT2A-rearranged AML and acute lymphoblastic leukemia as a category 2A treatment recommendation, signifying lower-level evidence but uniform consensus that treatment is appropriate.

Labeling warns of differentiation syndrome and notes numerous other possible adverse events, including QTc interval prolongation.

The recommended dose varies by weight and concomitant use of strong CYP3A4 inhibitors.

For instance, among patients weighing 40 kg or more who are also taking a strong CYP3A4 inhibitor, the dose is 160 mg twice daily.

The cost of thirty 160 mg tablets is $20,023.15, according to drugs.com.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape Medical News. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com.