Revumenib Joins NCCN Guidelines for NPM1-Mutated R/R Acute Myeloid Leukemia

The National Comprehensive Cancer Network (NCCN) has updated its Clinical Practice Guidelines in Oncology for Acute Myeloid Leukemia (AML) to include revumenib (Revuforj; Syndax Pharmaceuticals) as a category 2A recommendation for the treatment of patients with relapsed or refractory AML harboring an NPM1 mutation.1

The guideline update was supported by data from the phase 1/2 AUGMENT-101 trial (NCT04065399), which also supported the submission of a supplemental new drug application (sNDA) seeking the approval of revumenib for the treatment of patients with relapsed/refractory, NPM1-mutant AML.1,2 The FDA granted priority review to the sNDA and set a target action date of October 25, 2025, under the Prescription Drug User Fee Act.2

“The inclusion of revumenib as a recommended treatment option for relapsed/refractory, NPM1-mutated AML in the NCCN Guidelines underscores the strength of our clinical data in this population and further solidifies revumenib’s leading position,” Nick Botwood, MBBS, head of research & development and chief medical officer at Syndax Pharmaceuticals, stated in a news release.1 “Given the pivotal role NCCN Guidelines play in guiding the decision-making process for clinicians, payers, patients, and other key stakeholders in the US and beyond, this is a major milestone for Syndax and the entire acute leukemia community.”

What Were the Key AUGMENT-101 Findings for Revumenib in Relapsed/Refractory, NPM1-Mutant AML?

Findings from the open-label, dose-escalation and dose-expansion study published in Blood showed that adult patients with relapsed/refractory, NPM1-mutant AML (n = 64) achieved a complete response (CR) or CR with partial hematologic recovery (CRh) rate of 23.4% (95% CI, 13.8%-35.7%; 1-sided P = .0014).3 The composite CR (CRc) and overall response rate (ORR) in this population were 29.7% (95% CI, 18.9%-42.4%) and 46.9% (95% CI, 34.3%-59.8%), respectively.

Regarding safety (n = 84), any-grade treatment-emergent adverse effects (TEAEs) occurred in 98.8% of patients, including 91.7% who experienced grade 3 or higher TEAEs. The rates of any-grade and grade 3 or higher treatment-related AEs (TRAEs) were 78.6% and 59.5%, respectively. Overall, 76.2% of patients required dose reductions, and 66.7% of patients needed dose interruptions. TRAEs led to dose reductions in 11.9% of patients and treatment discontinuation in 4.8% of patients. One TRAE (cardiac arrest) led to death.

How Was the AUGMENT-101 Trial Designed?

The study enrolled adult and pediatric patients at least 30 days of age with relapsed/refractory acute leukemias harboring a documented NPM1 mutation or KMT2A rearrangement. Within the NPM1-mutated cohort, all patients enrolled were included in the safety analysis; the efficacy analysis included only patients with centrally confirmed NPM1 mutations and a bone marrow blast percentage of at least 5% within 28 days of the start of study treatment. There was no limit on the number of prior therapies. Patients with central nervous system (CNS) disease were allowed to enroll if there was no active CNS disease at screening.

The recommended phase 2 dose of revumenib was 270 mg every 12 hours (or 160 mg/m2 for patients under 40 kg), or 160 mg every 12 hours (or 95 mg/m2 for patients under 40 kg) if they were also receiving a strong CYP3A4 inhibitor. Treatment continued until lack of response after 4 cycles, disease progression, unacceptable toxicities, or consent withdrawal. Allogeneic hematopoietic stem cell transplant was permitted for patients who achieved a CRc, a morphological leukemia-free state, or a partial remission.

The CR plus CRh rate, along with safety, served as the trial’s primary end points. Secondary end points included CRc rate, ORR, time to response, duration of response, event-free survival, and overall survival.

Notably, prior data from AUGMENT-101 supported the November 2024 FDA approval of revumenib for the treatment of adult and pediatric patients 1 year of age and older with relapsed or refractory acute leukemia harboring a KMT2A translocation.4

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. News release. Syndax Pharmaceuticals. September 19, 2025. Accessed September 26, 2025. https://ir.syndax.com/news-releases/news-release-details/syndaxs-revuforjr-revumenib-included-nccn-clinical-practice
2. Syndax announces FDA priority review of sNDA for Revuforj (revumenib) in relapsed or refractory mNPM1 acute myeloid leukemia. News release. Syndax Pharmaceuticals. June 24, 2025. Accessed September 26, 2025. https://ir.syndax.com/news-releases/news-release-details/syndax-announces-fda-priority-review-snda-revuforjr-revumenib
3. 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
4. FDA approves revumenib for relapsed or refractory acute leukemia with a KMT2A translocation. FDA. November 15, 2024. Accessed September 26, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-revumenib-relapsed-or-refractory-acute-leukemia-kmt2a-translocation