Revumenib Granted FDA Approval for R/R NPM1-Mutated AML

The FDA has approved revumenib (Revuforj; Syndax Pharmaceuticals) for patients 1 year and older with relapsed or refractory acute myeloid leukemia with a susceptible nucleophosmin 1 (NPM1) mutation if there are no other satisfactory treatment options.¹

The approval was based on data from the phase 2 AUGMENT-101 (NCT04065399) trial, which found the rate of complete remission (CR) plus CR with partial hematological recovery (CRh) was 23.4% (95% CI, 13.8%-35.7%; P = .0014), according to the data published in May in Blood.² Updated data presented at the 2025 annual meeting of the European Hematology Association (EHA) in June showed a CR/CRh rate of 25%.³

According to the updated results presented at EHA, the median time to first CR/CRh was 2.8 months with a median duration of 4.7 months. The overall response rate was 48.1%.

“The expanded FDA approval of Revuforj marks a major advancement in the management of acute leukemia patients,” Joshua F. Zeidner, MD, chief, Leukemia Research at the University of North Carolina, Lineberger Comprehensive Cancer Center, said in a statement.⁴ “For the first time, a targeted, oral therapy that is well tolerated and efficacious is approved for R/R NPM1-mutated AML and R/R KMT2A-translocated acute leukemia. The compelling clinical activity observed with Revuforj in clinical trials and clinical practice paves the way for a new standard of care for these 2 aggressive and difficult-to-treat blood cancers.”

Examining Revumenib: Highlighting Efficacy and Adverse Events

The data published in Blood also showed that responses were observed across various subgroups, regardless of previous hematopoietic stem cell transplantation (HSCT) and number of lines of therapy.² CR/CRh rates were also similar among adults younger than 65 years or 65 years and older. Patients with previous venetoclax exposure had a CR/CRh rate of 16.7% (95% CI, 7.5%-30.2%), while patients without previous exposure had a CR/CRh rate of 43.8% (95% CI, 19.8%-70.1%).

There were 5 adult patients who achieved an overall response and underwent allogeneic HSCT while in remission, with 3 of them subsequently resuming revumenib after transplant.

In addition, 98.8% of patients experienced treatment-emergency adverse events (AEs), with 78.6% experiencing at least 1 treatment-related AE (TRAE) and 59.5% experiencing a grade 3 or higher TRAE.

Additional safety findings were:

• 76.2% of patients required a dose modification
• 66.7% of patients required a dose interruption
• 11.9% of patients requiring a dose reduction due to TRAEs
• The most common TRAEs were 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%)

“New treatment options are vitally needed for patients with NPM1-mutated AML whose disease has returned or not improved after previous treatment,” said Lore Gruenbaum, PhD, chief scientific officer of Blood Cancer United (formerly The Leukemia & Lymphoma Society). “The FDA approval of a precision treatment that selectively targets the pathway driving this form of AML offers new hope to patients and their loved ones.”

Revumenib was previously approved in 2024 to treat R/R acute leukemia with a KMT2A translocation for patients 1 year and older.⁵

References

1. FDA approves revumenib for relapsed or refractory acute myeloid leukemia with a susceptible NPM1 mutation. News release. FDA. October 24, 2025. Accessed October 24, 2025. https://www.cancernetwork.com/view/fda-approves-revumenib-in-r-r-npm1-mutant-aml

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. Published online May 7, 2025. Accessed May 8, 2025. doi:10.1182/blood.2025028357

3. Joszt L. Revumenib shows efficacy in patients with AML and genetic alterations. AJMC^®. June 12, 2025. Accessed October 24, 2025. https://www.ajmc.com/view/revumenib-shows-efficacy-in-patients-with-aml-and-genetic-alterations

4. Syndax announces FDA approval of Revuforj (revumenib) in adult and pediatric patients with relapsed or refractory NPM1 mutated acute myeloid leukemia. News release. Syndax Pharmaceuticals. October 24, 2025. Accessed October 24, 2025. https://ir.syndax.com/news-releases/news-release-details/syndax-announces-fda-approval-revuforjr-revumenib-adult-and

5. Rosa K. FDA approves revumenib for R/R acute leukemia with a KMT2A translocation. OncLive^®. November 15, 2204. Accessed October 24, 2025. https://www.onclive.com/view/fda-approves-revumenib-for-r-r-acute-leukemia-with-a-kmt2a-translocation