Clinical trialLeukaemia

Menin Inhibition With Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101)

J Clin Oncol · 202594 patients treated (57 patients evaluable for efficacy)

Issa GC, Aldoss I, Thirman MJ, et al. J Clin Oncol. 2025. 43:75-84

Study type: Clinical trial
Study name: AUGMENT-101
Design: Open-label, single-arm, dose-escalation and expansion study at 22 centres in 5 countries
Sample size: 94 patients treated (57 patients evaluable for efficacy)
Source: J Clin Oncol · 2025
Trial registration: NCT04065399

In plain words

Leukaemias with a KMT2A genetic change (previously called MLL) often do not respond to usual treatments. Revumenib is a tablet that blocks a protein called "menin" and so cuts off the growth pathway of these cancer cells. In this study of patients whose disease had come back, about two in every three people responded and about one in every five reached complete or near-complete remission; some patients were then able to have a bone marrow transplant. An important side effect called "differentiation syndrome" can occur, with fever and shortness of breath, and the care team must be told straight away.

Key results

22.8%

CR + CRh

95% CI 12.7 to 35.8; above the null hypothesis of 10% (P = .0036); 57 evaluable patients

63.2%

Overall response rate

95% CI 49.3 to 75.6

68.2%

MRD negativity among CR/CRh responders

15 of 22 patients

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, 163 mg (95 mg/m² if weight below 40 kg) with a strong CYP3A4 inhibitor, in 28-day cycles (trial dose).

FDA label dose: weight 40 kg or more: 270 mg twice daily without a strong CYP3A4 inhibitor and 160 mg twice daily with one; weight below 40 kg: 160 mg/m² (with a strong inhibitor: 95 mg/m²) twice daily. Start only with a white blood cell count below 25×10⁹/L; ECG before starting, weekly for the first 4 weeks and then monthly; at least 6 months of treatment in the absence of progression.

Source of the regimen details: Abstract of the paper (JCO 2025) and the FDA label for revumenib (DailyMed)

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

Children (from 30 days of age) and adults with relapsed or refractory acute leukaemia (myeloid, lymphoblastic or mixed lineage) with KMT2A (MLL) gene rearrangement. Median age 37 years (range 1.3 to 75). The separate NPM1-mutated AML cohort has been reported separately.

Endpoints

Primary endpoints: rate of complete remission or complete remission with partial haematological recovery (CR + CRh), and safety.

Secondary endpoints: overall response rate, measurable residual disease (MRD) negativity and duration of response.

Safety and side effects

Grade 3 or higher adverse events: febrile neutropenia 37.2%, differentiation syndrome 16.0% and QTc prolongation 13.8%. Differentiation syndrome (fever, dyspnoea, hypotension, fluid accumulation) requires prompt recognition and treatment with corticosteroids.

Clinical significance and place in guidelines

On the basis of this study, in November 2024 the FDA approved revumenib (Revuforj) as the first menin inhibitor for relapsed or refractory acute leukaemia with a KMT2A translocation in adults and children aged one year and older. In the NPM1-mutated AML cohort of the same trial (Blood 2025; 64 evaluable adult patients, 75% of whom had received prior venetoclax), the CR + CRh rate was 23.4% and the overall response rate 46.9%, with a median CR + CRh duration of 4.7 months, and on 24 October 2025 the FDA also approved revumenib for relapsed or refractory AML with a susceptible NPM1 mutation. Combinations of menin inhibitors with venetoclax/azacitidine or intensive chemotherapy in the first line are being studied in trials and are not yet approved.

Limitations

The study is single-arm with no comparator, and the primary endpoint is response rate, not survival. The complete remission rate is relatively limited and the duration of response is short in many patients; resistance through MEN1 gene mutations has been reported. Efficacy was assessed in only 57 patients with centrally confirmed KMT2Ar.

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.