REVUMENIB TAB
Clinical Criteria Summary
Document 836: MON Revumenib REVUFORJ Monograph Mar 2026
Indication
- Treatment of adults with relapsed/refractory (R/R) acute leukemia with a KMT2A rearrangement
- Treatment of R/R AML with a susceptible nucleophosmin 1 (NPM1) mutation in patients who have no satisfactory alternative treatment options
Patient Population & Disease Characteristics
- Adults (and pediatric patients down to 1 month per protocol amendment)
- Relapsed/refractory KMT2A rearranged acute leukemia, including AML, ALL, or mixed-phenotype acute leukemia (MPAL)
- NPM1-mutated AML
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0–2
- Exclusion: Patients with 11q23 partial tandem duplication (PTD)
- Inclusion: Patients with CNS disease at most recent relapse allowed if no active CNS disease remains present at study entry
Treatment Setting & Line of Therapy
- R/R acute leukemia
- Persistent acute leukemia despite at least 2 lines of therapy or relapse following the most recent salvage therapy
- No satisfactory alternative treatment options (specifically for NPM1-mutated AML)
Safety Monitoring & Initiation Criteria
- Differentiation syndrome: Prompt initiation of corticosteroid therapy and hemodynamic monitoring required
- QTc interval prolongation: Check ECG prior to start; do not initiate therapy with QTcF > 450 msec
- Electrolyte management: Correct electrolyte abnormalities (hypokalemia, hypomagnesemia) prior to and throughout treatment
- Embryofetal toxicity: Verify pregnancy status in females of reproductive potential within 7 days prior to initiating revumenib; use effective contraception during treatment and for 4 months after the last dose
- Lactation: Advise not to breastfeed during treatment and for 1 week after the last dose
Dosing & Administration Criteria
- Initial dosage depends on patient’s weight and CYP3A4 drug-interactions
- For body weights ≥ 40 kg: 270 mg PO twice daily without strong CYP3A4 inhibitors; 160 mg PO twice daily with strong CYP3A4 inhibitors
- Administer in a fasted state or with a low-fat meal (e.g., meals with about 400 calories, ≤ 25% fat)
- Tablets should be swallowed whole; if unable to swallow, may be crushed and dispersed in water and taken within 2 hours of preparation
- May be given until disease progression or unacceptable toxicity
- Dosage modifications required for differentiation syndrome and QTc interval prolongation per prescribing information
Drug Interaction Criteria
- Strong CYP3A4 inhibitors: Reduce revumenib dose
- Strong or moderate CYP3A4 inducers: Avoid concomitant use
- QTc prolonging drugs: Avoid concomitant use; if unavoidable, monitor patients more frequently
Contraindications
- None explicitly stated
Document 846: Revumenib REVUFORJ Criteria Mar 2026
Exclusion Criteria
- Presence of 11q23 partial tandem duplication (PTD)
- QTcF > 450 msec (Monitor more frequently for QTc interval prolongation if concomitant use of QTc prolonging drugs is unavoidable)
- Unmanageable drug-drug interaction (Reduce revumenib dose as recommended if concomitant strong CYP3A4 inhibitors are necessary)
- Pregnancy
- Lactating
- Inclusion Criteria (Select one)
- Relapsed or refractory acute leukemia with a lysine methyltransferase 2A gene (KMT2A) rearrangement; includes acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and mixed-phenotype acute leukemia (MPAL) (Defined as unresponsive to the most recent salvage therapy or persists despite intensive induction chemotherapy)
- Relapsed or refractory acute myeloid leukemia with NPM1-mutation
- Additional Inclusion Criteria (All must be fulfilled)
- Care is provided by a VA/VA Community Care hematology/oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status of 0–2
- Goals of care and role of Palliative Care consult have been discussed and documented
- White blood cell count less than 25 x 109/L before starting treatment due to risk of differentiation syndrome
- Reproductive & Contraceptive Requirements (If applicable)
- For females who can become pregnant: Pregnancy must be excluded prior to receiving revumenib.
- For females who can become pregnant and males with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 4 months after stopping treatment.