NCCN Recommends Revumenib for R/R NPM1+ Acute Myeloid Leukemia

Revumenib is FDA approved for use in adult and pediatric patients with KMT2A-mutated R/R AML.

The NCCN has added revumenib (Revuforj) to its guidelines for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML) harboring NPM1 mutations, according to a news release from Syndax Pharmaceuticals, Inc.¹

The first-in-class, oral menin inhibitor’s category 2A recommendation is supported by results from the open-label, dose-escalation, and dose-expansion phase 1/2 AUGMENT-101 trial (NCT04065399).^1,2

These results also support Syndax Pharmaceuticals’ supplemental new drug application (sNDA) for revumenib in the aforementioned indication.¹ The sNDA has been granted Priority Review with a target action date of October 25, 2025.

Revumenib is included in the NCCN’s guidelines for AML and acute myeloid lymphoblastic leukemia (ALL) as a category 2A recommendation for use in patents with relapsed or refractory acute leukemia with KMT2A mutations.

What Data Backs Revumenib’s Recommendation?

Data from AUGMENT-101 reported in Blood revealed that patients with relapsed or refractory NPM1-mutated AML experienced a complete remission (CR) with partial hematologic recovery (CRh; CR+CRh) rate of 23.4% (P = .0014) and an overall response rate (ORR) of 46.9%. The median duration of CR+CRh recovery was 4.7 months.

Most patients (83/84; 98.8%) experienced treatment-emergent adverse events (TEAEs). The most common TEAEs of any grade, occurring in at least 20% of patients, included QTcF prolongation (42.9%), vomiting (36.9%), febrile neutropenia (34.5%), hypokalemia (32.1%), nausea (28.6%), anemia (27.4%), diarrhea (27.4%), fatigue (23.8%), pyrexia (23.8%), epistaxis (21.4%), and peripheral edema (21.4%).

Four patients discontinued treatment due to treatment-related AEs (TRAEs), including cardiac arrest, differentiation syndrome, osteomyelitis, and QTcF prolongation along with syncope. One patient died from treatment-related cardiac arrest.

There were no restrictions on the quantity or variety of previous therapies used in the patient population. Patients received a capsule, tablet, or liquid formulation of revumenib every 12 hours in 28-day continuous cycles.

The dose of revumenib recommended for phase 2 of AUGMENT-101 was 270 mg for those with a bod weight of 40 kg or greater and 160 mg/m² for those weighing less than 40 kg given every 12 hours if patients were not receiving a strong CYP3A4 inhibitor. In patients also receiving a strong CYP3A4 inhibitor, the recommended dose was 160 mg for those weighing 40 kg or more and 95 mg/m² for those weighing less than 40 kg, given every 12 hours.

Patients received up to 4 cycles until lack of response, disease progression, or unacceptable toxicity.

Nursing Considerations for Menin Inhibitors

According to Ghayas C. Issa, MD, MS, who presented research on the use of the use of the menin inhibitor ziftomenib in NPM1-mutated AML at the 2025 SOHO Annual Meeting, differentiation is a class adverse effect of menin inhibitors that can become deadly.

Issa explained in an interview with Oncology Nursing News that differentiation syndrome is a reaction that occurs when menin inhibitors attack leukemia and in doing so produce proteins that irritate the lungs, kidneys, or heart.

“In dangerous scenarios, this could shut down the lungs and cause death,” explained Issa. “It’s very important to recognize differentiation syndrome, because physicians would start steroids, and in almost all the cases, by starting steroids early, we can prevent any complications from this syndrome.”

Is Revumenib FDA Approved?

Revumenib was approved for the treatment of adult and pediatric patients aged 1 year and older with relapsed or refractory acute leukemia and a KMT2A translocation on November 15, 2024, based on data from AUGMENT-101.³

This data showed a CR+CRh rate of 21,2 (95% CI, 13.8%-30.3%) with a median duration of 6.4 months (95% CI, 2.7-not estimable).

References

1. Syndax’s Revuforj® (revumenib) included in NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for the treatment of relapsed or refractory NPM1 mutated acute myeloid leukemia. Syndax Pharmaceuticals, Inc. News release. September 19, 2025. Accessed September 24, 2025. https://www.globenewswire.com/news-release/2025/09/19/3153072/0/en/Syndax-s-Revuforj-revumenib-Included-in-NCCN-Clinical-Practice-Guidelines-in-Oncology-NCCN-Guidelines-for-the-Treatment-of-Relapsed-or-Refractory-NPM1-Mutated-Acute-Myeloid-Leukemi.html
2. Arellano ML, Thirman MJ, DiPersio JF, et al. Menin inhibition with revumenib for NPM1-mutated relapsed or refractory acute myeloid leukemia: the AUGMENT-101 study. Blood. 2025;146(9):1065-1077. doi:10.1182/blood.2025028357
3. FDA approves revumenib for relapsed or refractory acute leukemia with a KMT2A translocation. FDA. November 15, 2024. Accessed September 24, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-revumenib-relapsed-or-refractory-acute-leukemia-kmt2a-translocation