Revumenib citrate, a menin inhibitor, is an antineoplastic agent.1
Acute Leukemia with KMT2A Translocation
Revumenib is used for the treatment of relapsed or refractory acute leukemia with a lysine methyltransferase 2A (KMT2A) translocation, as determined by an FDA-authorized test, in adults and pediatric patients 1 year of age and older.1
Revumenib has been designated an orphan drug by FDA for treatment of acute myeloid leukemia (AML), acute leukemias of ambiguous lineage, and acute lymphocytic leukemia (ALL).2
The efficacy of revumenib was evaluated in a single-arm cohort of an open-label, multicenter, phase 1/2 trial (AUGMENT-101), which included 104 patients with relapsed or refractory acute leukemia with a KMT2A translocation (without an 11q23 partial tandem duplication).1, 3, 4 To be eligible for the study, patients were required to have a baseline QT interval corrected using Fridericia's formula (QTcF) <450 msec.1, 3 Patients received revumenib orally twice daily with or without a strong cytochrome P-450 (CYP) 3A4 inhibitor until disease progression, unacceptable toxicity, failure to achieve a leukemia-free state by 4 cycles (112 days), or hematopoietic stem cell transplantation.1, 3 Revumenib was dosed without a strong CYP3A4 inhibitor at 270 mg orally twice daily (or 160 mg/m² twice daily for patients <40 kg) or with a strong CYP3A4 inhibitor at 160 mg twice daily (or 95 mg/m² twice daily for patients <40 kg).1, 3
The phase 1 portion of the study was an open-label, dose-escalation study with seven single-arm cohorts based on CYP3A4 inhibitor use, treatment schedule, and formulation.3 The phase 2 portion included three single-arm, disease-specific cohorts: KMT2A-rearranged ALL/mixed-phenotype acute leukemia (MPAL), KMT2A-rearranged AML, and NPM1-mutated AML.3, 4 Due to insufficient data confirming the reliability in selecting a representative patient population for the prespecified efficacy analysis, the FDA conducted an ad hoc analysis that included all patients completing the phase 1 and 2 trials who had acute leukemia with a KMT2A translocation, baseline marrow blasts ≥5%, and completed treatment with at least one dose of revumenib at the recommended dosage.3 The final cohort consisted of 79 adults and 25 children.3 The median age of patients was 37 years (range: 1-79); 76% were >17 years of age, 64% were female, 72% were White, 83% had AML, 15% had ALL, 2% had MPAL, 59% had relapsed disease, 53% had one prior relapse, and 44% had prior stem cell transplantation.1, 3
Efficacy of revumenib was based on the rate of complete remission (CR) plus CR with partial hematologic recovery (CRh), duration of response, and rate of conversion from transfusion dependence to independence; the median follow-up was 5.7 months (range: 0.3-28.9 months).1, 3 In the selected efficacy population, CR+CRh was achieved in 21% (22/104) of patients and the median duration of CR+CRh was 6.4 months.1 In subgroup analysis, CR+CRh was achieved in 21% of patients with AML, 19% of patients with ALL, and 50% of patients with MPAL.1, 3 Among 83 patients requiring RBC and/or platelet transfusions at baseline, 12 (14%) achieved transfusion independence during any 56-day post-baseline period, while 10 of 21 (48%) who were transfusion-independent at baseline remained so during any 56-day post-baseline period.1, 3 Remissions occurred in patients with refractory disease, were durable, and consistent across subpopulations.3
Acute Myeloid Leukemia with NPM1 Mutation
Revumenib is used for the treatment of relapsed or refractory acute myeloid leukemia (AML) with a susceptible nucleophosmin 1 (NPM1) mutation in adults and pediatric patients 1 year of age and older who have no satisfactory alternative treatment options.1
The efficacy of revumenib was evaluated in another single-arm cohort of the AUGMENT-101 trial, which included 65 patients with relapsed or refractory AML with a NPM1 mutation.1 The median age of patients was 65 years (range: 11-84); 1.5% were <17 years of age, 47.7% were 17 to <65 years of age, 50.8% were ≥65 years of age, 60% were female, 58.5% were White, and 23.1% had prior stem cell transplantation.1
Efficacy of revumenib was based on the rate of CR plus CRh, duration of response, and rate of conversion from transfusion dependence to independence; the median follow-up was 3.8 months (range: 0.1-29.9 months).1 In the selected efficacy population, CR+CRh was achieved in 23.1% (15/65) of patients and the median duration of CR+CRh was 4.5 months.1 Among 46 patients requiring RBC and/or platelet transfusions at baseline, 8 (17%) achieved transfusion independence during any 56-day post-baseline period, while 13 of 19 (68%) who were transfusion-independent at baseline remained so during any 56-day post-baseline period.1
Administer revumenib orally around the same time each day without food or with a low-fat meal (e.g., meal consisting of approximately 400 calories with <25% from fat).1
Swallow the tablets whole without cutting or chewing.1 If swallowing is difficult, the tablets may be crushed, mixed with water, and taken within 2 hours of preparation.1
Store the tablets at 20‒25°C; excursions between 15‒30°C are permitted.1
Revumenib is commercially available as the citrate salt; dosage is expressed in terms of revumenib.1
The recommended pediatric and adult dosage of revumenib for the treatment of relapsed or refractory acute leukemia with KMT2A translocation or acute myeloid leukemia with an NPM1 mutation is based on weight and whether or not the patient is receiving a concomitant strong cytochrome P-450 (CYP) 3A4 inhibitor.1
Patients ≥1 year of age weighing <40 kg who are not taking a strong CYP3A4 inhibitor: 160 mg/m² twice daily.1 See manufacturer's Prescribing Information for recommended total tablet dosage by BSA for patients weighing less than 40 kg.1
Patients ≥1 year of age weighing <40 kg who are taking a strong CYP3A4 inhibitor: 95 mg/m² twice daily.1 See manufacturer's prescribing Information for recommended total tablet dosage by BSA for patients weighing less than 40 kg.1
Patients ≥1 year of age weighing ≥40 kg who are not taking a strong CYP3A4 inhibitor: 270 mg twice daily.1
Patients ≥1 year of age weighing ≥40 kg who are taking a strong CYP3A4 inhibitor: 160 mg twice daily.1
Continue revumenib therapy until disease progression or unacceptable toxicity.1 If neither occurs, treat for at least 6 months to allow for a clinical response.1
If a strong CYP3A4 inhibitor is discontinued, wait at least 5 half-lives of the CYP3A4 inhibitor before increasing the revumenib dosage to the standard recommended dosage for patients not receiving a strong CYP3A4 inhibitor.1
If a revumenib dose is missed, take it as soon as possible the same day, at least 12 hours before the next dose.1 Resume the regular schedule the next day.1 Do not take 2 doses within 12 hours.1
Dosage Modification for Toxicity
If an adverse reaction occurs, treatment interruption, dosage reduction, and/or discontinuation of therapy may be necessary based on the severity of the adverse event.1
The manufacturer's recommended dosage reduction schedule and dosing modifications for adverse reactions are provided in Table 1 and the recommended dosage in Tables 2 and 3.1
Adverse Reaction | Recommended Action |
|---|---|
Differentiation syndrome | If suspected, administer systemic corticosteroids and monitor hemodynamics until symptoms resolve and for at least 3 days. Interrupt revumenib if severe symptoms persist >48 hours after starting systemic corticosteroids or sooner for life-threatening symptoms (e.g., pulmonary symptoms requiring ventilator support). Resume revumenib at the same dosage once symptoms improve to Grade ≤1. |
Noninfectious leukocytosis | Start hydroxyurea for elevated or rapidly rising leukocyte counts; add leukapheresis if clinically indicated. Taper hydroxyurea only after leukocytosis improves or resolves. |
QTc interval >480-500 msec | Interrupt revumenib, check electrolytes, and correct hypokalemia and hypomagnesemia. Restart revumenib at the same dosage once QTc≤480 msec. |
QTc >500 msec (Grade 3) | Interrupt revumenib, check electrolytes, and correct hypokalemia and hypomagnesemia. Restart revumenib at a reduced dosage after QTc≤480 msec (see Tables 2 and 3). |
QTc interval prolongation with signs/symptoms of life-threatening arrhythmia, torsades de pointes, polymorphic ventricular tachycardia, signs/symptoms of life-threatening arrhythmia (Grade 4) | Permanently discontinue revumenib. |
Potassium 3.6-3.9 mEq/L and/or magnesium 1.7-1.9 mg/dL | Supplement potassium and/or magnesium and continue revumenib therapy. |
Potassium ≤3.5 mEq/L and/or magnesium ≤1.6 mg/dL | Supplement potassium and/or magnesium and recheck levels within 24 hours. Hold revumenib, continue supplementation, and resume revumenib at the same dosage once correction is complete. |
Other nonhematological adverse reactions Grade ≥3 | Interrupt revumenib therapy until recovery to Grade 1 or baseline. If recovered in ≤7 days, restart revumenib at same dosage level. If the same Grade ≥3 toxicity recurs, interrupt revumenib until recovery to Grade 1 or baseline, then restart at a reduced dosage (see Tables 2 and 3). If recovered in >7 days, restart revumenib at the reduced dosage (see Tables 2 and 3). If the same Grade ≥3 toxicity recurs, discontinue revumenib. |
Neutropenia or thrombocytopenia Grade 4 | Interrupt revumenib until recovery to Grade ≤2 or baseline, then restart at the same dosage. If Grade 4 neutropenia or thrombocytopenia recurs without cause, interrupt until recovery to Grade ≤3 and restart at a reduced dosage (see Tables 2 and 3). |
Allergic reaction Grade ≥3 | Permanently discontinue revumenib. |
Patient Weighing ≥40 kg at Starting Dosage of 270 mg orally twice daily | Patients Weighing <40 kg at Starting Dosage of 160 mg/m2orally twice daily |
|---|---|
Reduce dosage to 160 mg orally twice daily. | Reduce dosage to 95 mg/m2 orally twice daily. |
Patients Weighing ≥40 kg at Starting Dosage of 160 mg orally twice daily | Patients Weighing <40 kg at Starting Dosage of 95 mg/m2orally twice daily |
|---|---|
Reduce dosage to 110 mg orally twice daily. | Reduce dosage to 65 mg/m2 orally twice daily. |
The manufacturer makes no recommendations on dosage adjustments for mild to moderate hepatic impairment.1 The effects of severe hepatic impairment have not been studied.1
The manufacturer makes no recommendations on dosage adjustments for mild to moderate renal impairment.1 The effects of severe renal impairment and end-stage renal disease have not been studied.1
The manufacturer makes no recommendations on dosage adjustments for geriatric patients.1
Revumenib can cause fatal or life-threatening differentiation syndrome; a boxed warning about this risk has been included in the prescribing information for the drug.1 Signs and symptoms of differentiation syndrome include fever, dyspnea, hypoxia, peripheral edema, pleuropericardial effusion, acute renal failure, rash, and/or hypotension.1
In clinical trials, differentiation syndrome occurred in 25% of 241 patients treated at the recommended dosage for relapsed or refractory acute leukemia.1 Among patients with a KMT2A translocation, differentiation syndrome occurred in 33% of patients with acute myeloid leukemia (AML), 33% of patients with mixed-phenotype acute leukemia (MPAL), and 9% of patients with acute lymphoblastic leukemia (ALL).1 Differentiation syndrome was reported in 18% of patients with NPM1-mutated AML.1 Grade 3 or 4 differentiation syndrome occurred in 12%, with two fatal cases.1 The median time to initial onset was 9 days (range: 3-41 days).1 Treatment interruption was required in 7% and discontinuation in 1%.1
Reduce WBC to <25 x 109 cells/L before initiating revumenib.1 If differentiation syndrome is suspected, immediately start systemic corticosteroids (e.g., dexamethasone 10 mg IV every 12 hours in adults or in pediatric patients <40 kg, 0.25 mg/kg IV every 12 hours) for at least 3 days until symptoms resolve.1 Provide supportive care and hemodynamic monitoring.1 Interrupt revumenib if severe symptoms persist >48 hours despite therapy with corticosteroids or earlier if life-threatening symptoms occur (e.g., need for ventilatory support).1 Restart corticosteroids if differentiation syndrome recurs after tapering.1
QTc Prolongation and Torsades de Pointes
Revumenib can cause QTc interval prolongation and torsades de pointes; a boxed warning regarding this risk is included in the prescribing information.1 In clinical trials, QTc prolongation occurred in 36% of 241 patients treated at the recommended dosage, including Grade 3 prolongation in 15% and Grade 4 in 2%.1 QTc prolongation occurred in 21% of those <17 years of age, 35% in 17‒65 years of age, and 46% in ≥65 years of age.1 QTcF (QT interval corrected for heart rate using Fridericia's formula) exceeded 500 msec in 10%, and QTcF increased by >60 msec from baseline in 24%.1 Dosage reduction due to QTc prolongation was required in 7% of patients.1 A single patient had a fatal cardiac arrest and one patient experienced nonsustained torsades de pointes.1
Correct electrolyte abnormalities, including hypokalemia and hypomagnesemia, before starting revumenib and throughout therapy.1 Obtain an ECG before initiation and do not start treatment if QTcF >450 msec.1 Perform ECGs at least weekly for the first 4 weeks, then at least monthly.1 More frequent monitoring may be needed in patients with congenital long QT syndrome, heart failure, electrolyte imbalances, or those on QTc prolonging drugs.1 Concomitant use with QTc prolonging medications may increase risk.1 Interrupt revumenib therapy if QTcF increases to 480-500 msec, and resume at the same dosage once QTcF returns to ≤480 msec.1 If QTcF >500 msec or increases by >60 msec from baseline, interrupt revumenib therapy and restart at a lower dosage once QTcF returns to ≤480 msec.1 Permanently discontinue revumenib in patients with ventricular arrhythmias or QTc prolongation with life-threatening arrhythmic symptoms.1
Other Warnings and Precautions
Fetal/Neonatal Morbidity and Mortality
Based on animal studies and its mechanism of action, revumenib may cause fetal harm if administered during pregnancy.1 In animal studies, oral revumenib exposure during organogenesis caused embryo-fetal mortality, malformations, and impaired fetal growth at maternal drug exposures approximately half of those observed in humans at the recommended dose based on AUC comparisons.1
Advise pregnant women of the potential fetal risk.1 Counsel females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for 4 months after the last dose.
Based on animal studies and its mechanism of action, revumenib may cause fetal harm if administered during pregnancy.1 No human data are available to assess drug-associated risk.1 In animal studies, oral revumenib exposure during organogenesis caused embryo-fetal mortality, malformations, and impaired fetal growth at maternal drug exposures approximately half of those observed in humans at the recommended dose based on AUC comparisons.1 Advise pregnant women of the potential fetal risk.1
There are no data on the presence of revumenib or its metabolites in human milk or effects on the breastfed child or milk production.1 Due to the potential for serious adverse reactions, advise women not to breastfeed during treatment and for 1 week after the last dose.1
Females and Males of Reproductive Potential
Based on findings in animals and its mechanism of action, revumenib can cause fetal harm when administered to pregnant women and may impair fertility.1 Verify pregnancy status in females of reproductive potential within 7 days of beginning therapy with revumenib.1
Advise females and males of reproductive potential to use effective contraception during treatment with revumenib and for 4 months after the last dose.1
The safety and efficacy of revumenib have been established in pediatric patients ≥1 year of age with relapsed or refractory acute leukemia with a KMT2A translocation or an NPM1 mutation.1 This is supported by data in adults and pediatric patients, along with additional pharmacokinetic and safety data.1 The study population included 25 infants (<2 years of age), 78 children (2 to <12 years of age), and 29 adolescents (12 to <17 years of age).1 The safety and efficacy of revumenib in patients <1 year of age have not been established.1
In clinical studies of revumenib, 61 (25%) of 241 patients with relapsed or refractory acute leukemia with a KMT2A translocation or an NPM1 mutation were ≥65 years of age, and 25 (10%) were ≥75 years of age.1 No overall differences in efficacy were observed between patients ≥65 years of age and younger patients.1 However, QTc prolongation and edema occurred more frequently in patients ≥65 years of age.1
No significant pharmacokinetic differences have been observed in patients with mild to moderate hepatic impairment; effects of severe hepatic impairment are unknown.1
No significant pharmacokinetic differences have been observed in patients with mild to moderate renal impairment; effects of severe renal impairment or end-stage renal disease are unknown.1
The most common adverse reactions (≥20%) with revumenib, including laboratory abnormalities, are increased phosphate, hemorrhage, nausea, infection without identifed pathogen, increased AST, increased ALT, increased creatinine, musculoskeletal pain, febrile neutropenia, QT prolongation, decreased potatssium, increased intact parathyroid hormone, increased alkaline phosphatase, diarrhea, bacterial infection, increased triglycerides, differentiation syndrome, fatigue, edema, viral infection, decreased phosphate, decreased appetite, and constipation.1
Revumenib is primarily metabolized by cytochrome P-450 (CYP) 3A4.1 Revumenib inhibits CYP3A4, but does not inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP2E1.1 Revumenib does not induce CYP1A2, CYP2B6, and CYP3A4.1
Revumenib is a substrate of organic cation transporter 1 (OCT1), OCT2, and OAT3, as well as multidrug and toxin extrusion protein 1 (MATE1), but is not a substrate of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptide 1B1 (OATP1B1) and OATP1B3, MATE2-K, or bile salt export pump (BSEP).1
M1, a metabolite of revumenib, is a substrate of OATP1B1 but not of P-gp, BCRP, OCT2, OAT1, OAT3, OATP1B3, MATE1, or MATE2-K.1
Revumenib inhibits MATE1 but does not inhibit P-gp, BCRP, OCT1, OCT2, OAT1, OAT3, OATP1B1, OATP1B3, BSEP, or MATE2-K.1 M1 inhibits MATE1 but does not inhibit OAT1, OAT3, OCT2, OATP1B1, OATP1B3, or MATE2-K.1
Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes
If concomitant use of revumenib and a strong CYP3A4 inhibitor is required, reduce the revumenib dosage.1 Concomitant administration of multiple doses of revumenib with strong CYP3A4 inhibitors such as certain azole antifungals (i.e., posaconazole, itraconazole, voriconazole) increased revumenib peak plasma concentrations and AUC by 2-fold; in addition, co-administration with cobicistat (another strong CYP3A4 inhibitor) increased peak plasma concentrations and AUC of revumenib by 2.5-fold.1 No clinically significant differences in revumenib pharmacokinetics were observed when administered concomitantly with moderate CYP3A4 inhibitors (i.e., fluconazole, isavuconazole).1
Avoid concomitant use of revumenib with strong or moderate CYP3A4 inducers.1 Coadministration with CYP3A4 inducers may decrease revumenib exposure and increase the metabolite exposure (M1), which could reduce drug efficacy or increase the risk of QT prolongation associated with the metabolite.1
Drugs Associated with QT Prolongation
Revumenib prolongs the QTc interval, and co-administration with QTc-prolonging drugs may further increase QTc and the risk of related adverse effects.1
Avoid concomitant use of revumenib with drugs known to prolong the QTc interval.1 If unavoidable, monitor ECG at initiation, during concomitant use, and as clinically indicated.1 Withhold revumenib if QTc >480 msec and restart once QTc returns to ≤480 msec.1
Revumenib is a menin inhibitor that blocks the interaction of wild-type lysine methyltransferase 2A (KMT2A) and KMT2A fusion proteins with menin.1 The binding of wild-type KMT2A or KMT2A fusion proteins with menin is involved in NPM1 mutated acute myeloid leukemias and KMT2A rearranged acute leukemias, respectively, through activation of a leukemogenic transcriptional pathway.1 Susceptible NPM1 mutations are defined as those that result in loss of the nucleolar localization signal and the insertion of a new nuclear export signal leading to the accumulation of mutant NPM1 in the cytoplasm of AML cells.1 The most common of such NPM1 mutations in patients with AML are Types A, B, and D.1 In nonclinical studies, revumenib disrupted menin-KMT2A binding, altering gene transcription, including differentiation markers.1 In vitro and in vivo nonclinical studies showed that revumenib has antiproliferative and antitumor activity in leukemia cells with KMT2A fusions.1 Revumenib also has antiproliferative activity in vitro in leukemic cells with an NPM1 mutation.1
In patients with relapsed or refractory acute leukemia, revumenib exhibits dose-proportional pharmacokinetics over a dosage range of 113‒339 mg twice daily.1 Steady-state concentrations are achieved within 2 days.1 The median time to peak concentration is 2 hours (range: 0‒12 hours) when administered concomitantly with strong CYP3A4 inhibitors and 1 hour (range: 0.5‒4 hours) without such inhibitors.1 Administration with a low fat meal did not significantly affect revumenib exposure.1 Revumenib has 90% protein binding and a blood-to-plasma ratio of 0.8.1 The elimination half-life is 6.4 hours with strong CYP3A4 inhibitors and 3 hours without inhibitors.1 Revumenib is primarily metabolized by CYP3A4, producing an active metabolite, M1.1 Excretion occurs via feces (approximately 52%, with 7% as unchanged drug) and urine (approximately 25%, with 6% as unchanged drug).1
Revumenib pharmacokinetics showed no clinically significant differences based on age (1‒84 years of age), race (67% White, 7% Asian, 8% Black), or sex.1 Body weight (6-151 kg) significantly affects revumenib pharmacokinetics, with higher exposure in patients <40 kg, supporting BSA-based dosing for this group.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Revumenib is available through the designated specialty pharmacy, SyndAccess. Consult the SyndAccess website ([Web]) or the revumenib website ([Web]) for more information.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 25 mg (of revumenib) | Revuforj® | Syndax Pharmaceuticals |
110 mg (of revumenib) | Revuforj® | Syndax Pharmaceuticals | ||
160 mg (of revumenib) | Revuforj® | Syndax Pharmaceuticals |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions August 10, 2026. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Syndax Pharmaceuticals, Inc. Revuforj® (revumenib) ORAL prescribing information. 2026 Feb. [Web]
2. Food and Drug Administration. Search Orphan Drug Designations and Approvals. Silver Spring, MD. From FDA website. Accessed 2025 Feb 21. [Web]
3. Food and Drug Administration. Center for Drug Evaluation and Research. Application number 218944Orig1s000: Multi-Discipline Review.[Web] [Web]
4. Issa GC, Aldoss I, Thirman MJ, et al. Menin inhibition with revumenib for KMT2A-rearranged relapsed or refractory acute leukemia (AUGMENT-101). J Clin Oncol. 2025;43(1):75-84. [Web]