NCCN recommends Revumenib-Revuforj for R/R NPM1+ acute myeloid leukemia

NCCN has added Revumenib-Revuforj to its guidelines for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML) harboring NPM1 mutations. Open-label, dose-escalation and dose-expansionResults from the Phase 1/2 AUGMENT-101 trial (NCT04065399) support category 2A recommendations for first-in-class oral menin inhibitors. These results also support Syndax Pharmaceuticals' supplemental New Drug Application (sNDA) for revumenib in the above indications.

Revimenib is included in the NCCN acute myeloid and acute lymphoblastic leukemia (ALL) guidelines as a category 2A recommendation for patients with relapsed or refractory acute leukemia with KMT2A mutations. AUGMENT-101 data showed that patients with relapsed or refractory NPM1-mutated AML experienced complete remission (CR), partial hematological recovery (CRh; CR+CRh) rate of 23.4% (P=0.0014), and overall response rate (ORR) of 46.9%. The median duration of recovery from CR+CRh was 4.7 months.

The majority of patients (83/84; 98.8%) experienced a treatment-emergent adverse event (TEAE). 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%), fever (23.8%), epistaxis (21.4%) and peripheral edema (21.4%, 21.4%).

Four patients discontinued treatment due to treatment-related adverse events (TRAEs), including cardiac arrest, differentiation syndrome, osteomyelitis and QTcF prolongation, and syncope. One patient died from treatment-related cardiac arrest. There is no limit on the number or type of prior therapies used in the patient population. Patients received revumenib capsules, tablets, or liquid every 12 hours in consecutive 28-day cycles.

The recommended revumenib dose for Phase 2 of AUGMENT-101 is 270 mg for patients weighing 40 kg or more and 160 mg/m for patients weighing less than 40 kg, or every 12 hours if the patient is not receiving a strong CYP3A4 inhibitor. In patients receiving concurrent strong CYP3A4 inhibitors, the recommended dose is 160 mg for patients weighing 40 kg or more and 95 mg/m2 for patients weighing less than 40 kg, administered every 12 hours.

Patients received up to4 cycles of treatment until lack of response, disease progression, or unacceptable toxicity.

Research on the use of menininhibitorziftomenib in NPM1-mutated AML was introduced at the 2025 SOHO Annual Meeting. Differentiation syndrome is a type of adverse reaction ofmenin inhibitors that may become fatal. Differentiation syndrome is a reaction that occurs when leukemia is attacked by an inhibitor, in this case producing proteins that irritate the lungs, kidneys or heart.

In dangerous cases, this can close the lungs and lead to death. Recognizing differentiation syndrome is important because doctors will initiate steroids, and in almost all cases, by using steroids early, we can prevent any complications of this syndrome.

Based on data from AUGMENT-101.3, Revumenib was approved on November 15, 2024 for the treatment of adult and pediatric patients 1 year and older with relapsed or refractory acute leukemia and KMT2A translocation. The data showed thatCR+CRh rate was 21.2 (95%CI, 13.8%-30.3%), and the median duration was 6.4 months (95%CI: 2.7-not estimable).

Reference materials:https://www.oncnursingnews.com/view/nccn-recommends-revumenib-for-r-r-npm1-acute-myeloid-leukemia