Clinical trialLeukaemia

Menin inhibition with revumenib for NPM1 -mutated relapsed or refractory acute myeloid leukemia: the AUGMENT-101 study

Blood · 202584 patients who received at least one dose of revumenib; 64 adult patients in the efficacy-evaluable population for the primary analysis

Arellano ML, Thirman MJ, DiPersio JF, Heiblig M, Stein EM, Schuh AC, et al. Blood. 2025. 146:1065-1077

Study type: Clinical trial
Study name: AUGMENT-101
Design: Analysis of the phase 2 portion of the phase 1/2 AUGMENT-101 study; all enrolled patients received revumenib and no comparator group is mentioned in the abstract
Sample size: 84 patients who received at least one dose of revumenib; 64 adult patients in the efficacy-evaluable population for the primary analysis
Source: Blood · 2025
Trial registration: NCT04065399

In plain words

Acute myeloid leukaemia with an NPM1 mutation has limited treatment options when it comes back after treatment or does not respond to treatment. In this study, the oral medicine revumenib, which blocks the menin protein, was given to patients who had already had many treatments. About a quarter of patients reached complete or almost complete remission, and some of them were able to have a stem cell transplant. Side effects led to stopping the medicine in fewer than 5% of patients.

Key results

23.4%

CR + CRh rate (64 evaluable adult patients)

One-sided P = 0.0014

46.9%

Overall response rate (ORR)

4.7 months

Median duration of CR + CRh

5 of 30 responders (16.7%)

Haematopoietic stem cell transplantation (HSCT) among responders

3 restarted revumenib after HSCT

Dose and schedule cards

Revumenib (AUGMENT-101)

Relapsed or refractory acute leukaemia with a KMT2A translocation (aged 1 year and older), or relapsed or refractory NPM1-mutated AML with no other satisfactory optionCycle length: ContinuousOn the page “Leukaemia” · Regimens and dosing in relapsed or refractory AML

Relapsed or refractory acute leukaemia with a KMT2A translocation (aged 1 year and older), or relapsed or refractory NPM1-mutated AML with no other satisfactory option

Drug	Dose	Route	Schedule
Weight 40 kg or more
Revumenib	270 mg twice daily (with a strong CYP3A4 inhibitor: 160 mg twice daily)	Oral, on an empty stomach or with a low-fat meal	Continuous
Weight less than 40 kg
Revumenib	160 mg/m² twice daily (with a strong CYP3A4 inhibitor: 95 mg/m²)	Oral	Continuous

Cycle length: Continuous
Duration: Until progression or unacceptable toxicity; in the absence of progression, at least 6 months to allow time for a response

ECG before starting, at least weekly for the first 4 weeks and then monthly (QTc prolongation); blood counts, electrolytes and liver enzymes before starting and monthly. Differentiation syndrome is an important adverse effect (grade ≥3 in 16.0% in AUGMENT-101); grade ≥3 QTc prolongation occurred in 13.8%. In patients at risk of central nervous system relapse, concurrent intrathecal prophylaxis is recommended.

On the page “Leukaemia” · Regimens and dosing in relapsed or refractory AML

Revumenib (AUGMENT-101)

Relapsed or refractory acute leukaemia with a KMT2A translocation (age 1 and over), or relapsed or refractory NPM1-mutated AML with no satisfactory alternativeCycle length: ContinuousOn the page “Acute myeloid leukaemia (AML): 2022 classification, ELN genetic risk and treatment” · Targeted treatment in relapsed or refractory AML

Relapsed or refractory acute leukaemia with a KMT2A translocation (age 1 and over), or relapsed or refractory NPM1-mutated AML with no satisfactory alternative

Drug	Dose	Route	Schedule
Weight 40 kg or more
Revumenib	270 mg twice a day (with a strong CYP3A4 inhibitor: 160 mg twice a day)	Oral	Continuous
Weight below 40 kg
Revumenib	160 mg/m² twice a day (with a strong CYP3A4 inhibitor: 95 mg/m²)	Oral	Continuous

Cycle length: Continuous
Duration: At least 6 months in the absence of progression

Boxed warning for differentiation syndrome and QTc prolongation and torsade de pointes; do not start with QTcF above 450. ECG before starting, at least weekly for the first 4 weeks and then monthly; blood counts, electrolytes and liver enzymes before starting and monthly. In the KMT2A cohort, grade ≥3 differentiation syndrome occurred in 16.0% and grade ≥3 QTc prolongation in 13.8%.

On the page “Acute myeloid leukaemia (AML): 2022 classification, ELN genetic risk and treatment” · Targeted treatment in relapsed or refractory AML

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Revumenib (single arm)

Revumenib orally every 12 hours with or without a strong CYP3A4 inhibitor, in 28-day cycles (exact trial dose not given in the abstract).

FDA label dose for relapsed or refractory NPM1-mutated AML: weight 40 kg or more: 270 mg twice daily (with a strong CYP3A4 inhibitor: 160 mg twice daily); below 40 kg: 160 mg/m² (95 mg/m² with a strong inhibitor) twice daily; fasting or with a low-fat meal; until progression or toxicity, and for at least 6 months in the absence of progression.

Source of the regimen details: Abstract of the paper (every-12-hour schedule in 28-day cycles) and the FDA label for revumenib (DailyMed) for the approved dose

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with relapsed or refractory (R/R) acute myeloid leukaemia (AML) with a nucleophosmin 1 mutation (NPM1m) in the phase 2 portion of AUGMENT-101. Median age 63 years, and one patient was younger than 18. Protocol-defined efficacy-evaluable population: 64 adult patients (35.9% with at least 3 prior lines of therapy and 75.0% with prior venetoclax).

Endpoints

Primary endpoints: rate of complete remission (CR) or complete remission with partial haematological recovery (CRh) (CR + CRh), safety and tolerability. Secondary endpoints: overall response rate (ORR) and duration of response.

Safety and side effects

Treatment-related adverse events led to discontinuation in 4 patients (4.8%). The safety profile of revumenib was consistent with previously reported results. Exact rates of grade 3 and higher adverse events are not given in the abstract.

Clinical significance and place in guidelines

These results show that menin inhibition with revumenib can produce clinically meaningful responses in relapsed or refractory NPM1-mutated AML and, in some patients, enable stem cell transplantation. According to the abstract, revumenib had previously been approved for R/R acute leukaemia with a KMT2A translocation in patients aged 1 year and older. The formal approval status and place of this drug in NPM1m AML are not stated in the abstract and should be checked in current guidelines and regulatory sources.

Limitations

According to the abstract, the study had no comparator control group (all patients received revumenib). The median duration of response (CR + CRh) was relatively short at 4.7 months. Overall survival results are not reported in the abstract. The primary analysis included 64 adult patients. Authors from the drug's manufacturer (Syndax) took part in the study.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.