CurrentHealth NetPolicy CP PHAR.707

Clinical Policy: Revumenib (Revuforj)

Defines medical necessity criteria, dosing guidance, and authorization requirements for Revumenib (Revuforj) for commercial, HIM, and Medicaid members; applies to providers prescribing or seeking coverage for this drug.

Policy Summary

PayerHealth Net

PolicyClinical Policy: Revumenib (Revuforj)

Policy CodePolicy CP PHAR.707

Change TypeNo material change

Effective DateMar 1, 2025

Next Review Date

Key ActionProvider must submit documentation (office chart notes, lab results, or other clinical information) supporting that the member has met all approval criteria.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

Age ≥ 1 yearminimum approved patient age

6 monthsinitial authorization length

25, 110, 160 mgproduct strengths

Boxed warningsafety alert

State precedenceMedicaid note

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage Criteria for Revumenib (Revuforj)

inv-01: Initial Approval Criteria

Covered when ALL of the following are met

Initial approval for Revumenib: 1) Diagnosis of relapsed or refractory acute leukemia (e.g., acute myeloid leukemia [AML], acute lymphoblastic leukemia [ALL], or mixed phenotype acute leukemia [MPAL]); 2) Prescribed by or in consultation with an oncologist or hematologist; 3) Age ≥ 1 year; 4) Disease is positive for a KMT2A gene translocation; 5) For Revuforj requests, member must use revumenib (Revuforj) if available unless contraindicated or clinically significant adverse effects are experienced; 6) Request meets one of the following: a) Member weight ≥ 40 kg and both of the following: i) Dose does not exceed the specified limits (maximum 540 mg per day; for weight ≥ 40 kg a recommended regimen includes 160 mg/day as described in the Dosage and Administration section) and ii) dose formulation limits (no more than 4 tablets per day); OR b) Prescribed dose is supported by practice guidelines or peer-reviewed literature for the relevant off‑label use with prescriber submission of supporting evidence; 7) Prescribed regimen must be FDA‑approved or recommended by NCCN for the indication or be supported as described above.see node text

Approval duration: 6 months

inv-02: Continuation Therapy

Covered when ALL of the following are met for ongoing therapy

Continuation criteria: 1) Member is currently receiving Revuforj via the Centene benefit, or documentation supports that the member has been receiving Revuforj for a covered indication for at least 30 days; 2) Member is responding positively to therapy; 3) For Revuforj requests, member must use revumenib (Revuforj) if available unless contraindicated or clinically significant adverse effects are experienced; 4) If request is for a dose increase, the request meets one of the following: a) Dose does not exceed the specified limits (maximum 540 mg per day; for weight ≥ 40 kg recommended regimen includes 160 mg/day and formulation limit of up to 4 tablets per day); OR b) New dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use with prescriber submission of supporting evidence; 5) Prescribed regimen must be FDA‑approved or recommended by NCCN.see node text

Requests for use of Revumenib (Revuforj) for non‑FDA approved indications that are not expressly addressed in this policy are excluded from coverage unless the provider supplies sufficient documentation of efficacy and safety. Documentation must meet the applicable off‑label use policy standards (see policies CP.CPA.09 for commercial, HIM.PA.154 for Health Insurance Marketplace, and CP.PMN.53 for Medicaid) or be supported by evidence of coverage provisions.

When coverage provisions in this clinical policy conflict with state Medicaid program requirements, the state Medicaid coverage provisions take precedence. Providers should refer to the applicable state Medicaid manual for specific coverage rules that supersede this policy for Medicaid members.

Initial Therapy Eligibility

inv-18: Initial Therapy

Initial therapy coverage criteria

Initial therapy nodes: Diagnosis of relapsed or refractory acute leukemia (AML, ALL, MPAL); prescribed by or in consultation with an oncologist or hematologist; age ≥ 1 year; disease positive for KMT2A gene translocation; member must use Revuforj if available unless contraindicated or significant adverse effects occur; dosing consistent with weight categories (weight ≥ 40 kg dosing tiers) and does not exceed specified maximums (maximum 540 mg/day and formulation limit of 4 tablets/day) or, if outside these limits, is supported by practice guidelines or peer‑reviewed literature with prescriber evidence submission; prescribed regimen must be FDA‑approved or recommended by NCCN.

Continuation Therapy Eligibility

inv-19: Continuation

Continuation therapy requirements for members already receiving Revuforj

Continuation therapy nodes: Member has taken Revuforj for ≥ 30 days and is receiving it through the Centene benefit or has documentation supporting current use; member is responding positively to therapy; if a dose increase is requested, the new dose must not exceed specified limits (maximum 540 mg/day; for weight ≥ 40 kg recommended regimen includes 160 mg/day and up to 4 tablets/day) or the increase must be supported by practice guidelines or peer‑reviewed literature with prescriber supporting evidence; member must use Revuforj if available unless contraindicated or clinically significant adverse effects are experienced; prescribed regimen must be FDA‑approved or NCCN‑recommended.

Dosing & Coding Considerations

inv-05: Weight threshold — 40 kg (dosing tiers and recommendations vary by weight and concomitant strong CYP3A4 inhibitor use)

Weight threshold40 kg — dosing tiers and recommended regimens are defined starting at 40 kg; dosing varies by weight and concomitant strong CYP3A4 inhibitor use.

Dosing basisDosing recommendations use body surface area (BSA) calculations for patients at the 40 kg threshold and across weight tiers.

Strong CYP3A4 inhibitor considerationDose recommendations differ when strong CYP3A4 inhibitors are coadministered (examples: posaconazole, itraconazole, voriconazole).

Dose examplesDocumented dosing tiers include tablet doses (25 mg, 50 mg, 75 mg, 110 mg, 135 mg, 160 mg) mapped to weight/BSA categories in the product dosing tables.

Provider Actions, Prior Authorization & Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must submit documentation (such as office chart notes, laboratory results, or other clinical information) that demonstrates the member meets all approval criteria. Approval criteria include diagnosis of relapsed or refractory acute leukemia (eg, AML, ALL, MPAL), documented KMT2A (KMT2A) gene translocation, prescription by or in consultation with an oncologist or hematologist, and age ≥ 1 year. For Revuforj requests, member must use revumenib (Revuforj) when available unless contraindicated or clinically significant adverse effects occur. Dose requests (including dose increases) must meet the policy dose limits or be supported by practice guidelines or peer-reviewed literature; weight-based dosing and tablet limits apply (see policy dosage guidance). Prescribed regimen must be FDA-approved or recommended by NCCN for the requested indication. Approval duration for initial authorizations is 6 months. Continued therapy requires documentation that the member has received the medication for at least 30 days and is responding positively to therapy. Providers must submit supporting evidence when seeking doses or regimens for non‑FDA or off‑label uses.

Submit: office chart notes, lab results, other clinical information verifying all approval criteria
Required diagnosis: relapsed or refractory acute leukemia (AML, ALL, MPAL)
Required biomarker: positive KMT2A gene translocation
Prescriber: oncologist or hematologist (or in consultation with one)
Age: ≥ 1 year
Revuforj-specific: member must use revumenib (Revuforj) when available unless contraindicated or intolerant
Dosing constraints: must not exceed policy dose limits (eg, up to 540 mg/day or tablet limits as specified) or must be supported by practice guidelines/peer-reviewed literature for off‑label regimens
Regimen support: prescribed regimen must be FDA‑approved or recommended by NCCN; for off‑label use, submit supporting evidence
Initial approval duration: 6 months
Continuation requirements: ≥30 days of therapy documented and positive response to therapy; dose increases require justification per dosing rules
Non‑FDA indications: will be denied unless sufficient documentation of efficacy/safety per applicable off‑label use policies (CP.CPA.09, HIM.PA.154, CP.PMN.53 or evidence of coverage) is provided
Contractual notice: providers, members, and representatives are bound by policy terms; unauthorized copying or distribution prohibited

Denial Risk

Non‑FDA Indications

Requests for non‑FDA approved indications that are not specifically addressed in this policy will be denied unless the prescriber submits sufficient documentation demonstrating efficacy and safety consistent with the plan's off‑label use policies (see CP.CPA.09 for commercial, HIM.PA.154 for Health Insurance Marketplace, and CP.PMN.53 for Medicaid) or other applicable evidence of coverage provisions. Supporting documentation should include practice guidelines, peer‑reviewed literature, and any other clinical rationale.

Off‑label requests must include supporting evidence (guidelines, peer‑reviewed literature, clinical rationale)
Refer to applicable off‑label policies: CP.CPA.09 (Commercial), HIM.PA.154 (Marketplace), CP.PMN.53 (Medicaid)

Documentation Required

Use of Revumenib and Dose Change Requirements

When Revuforj (revumenib) is requested, member must use revumenib when it is available and not contraindicated. Dose changes or increases require documentation that the new dose does not exceed policy limits (for example, up to 540 mg per day or tablet limits noted in dosing guidance) or is supported by established practice guidelines or peer‑reviewed literature. For weight-based dosing, follow the policy's dosing references (including weight thresholds such as ≥ 40 kg where applicable). Prescribers must submit evidence when a requested dose or regimen differs from FDA‑approved dosing or NCCN recommendations.

Member must use revumenib (Revuforj) when available unless contraindicated or clinically significant adverse effects occur
Dose increases require documentation meeting policy dose limits or guideline/literature support
Weight-based dosing considerations apply (eg, thresholds at 40 kg); see Dosage and Administration section
Prescriber must provide supporting evidence for non‑standard dosing/regimens

Step Therapy

There are no step therapy requirements specified in this policy excerpt.

No step therapy applies per the available policy content

Note

Contractual and Use Notice

Providers, members, and their representatives are bound to the terms and conditions of this clinical policy by contract or by providing services/submitting claims. Unauthorized copying, use, distribution, or breach of the policy terms is prohibited and may result in denial of requests or other contractual remedies.

By submitting requests or claims, providers agree to be bound by policy terms
Unauthorized use or distribution of the clinical policy is prohibited

Background on Revumenib (Revuforj)

Revumenib (Revuforj) is a menin inhibitor indicated for the treatment of relapsed or refractory acute leukemia harboring KMT2A (MLL) gene translocations in adults and pediatric patients aged 1 year and older. The product carries a boxed warning for differentiation syndrome, and dosing recommendations vary by patient weight (notably dosing tiers for patients ≥ 40 kg) and by concomitant use of strong CYP3A4 inhibitors. Tablet strengths available include 25 mg, 110 mg, and 160 mg.

Key Definitions

inv-15: Differentiation syndrome — A potentially serious adverse event listed as a boxed warning for Revumenib; monitoring and management per product labeling are required.

DefinitionDifferentiation syndrome — a potentially serious adverse event and boxed warning for Revumenib; monitoring and management are required per product labeling.

Regulatory statusListed as a boxed warning in the product safety information (Appendix C).

Clinical implicationProviders must monitor for signs/symptoms and manage according to labeled guidance to mitigate serious outcomes.

inv-16: KMT2A gene translocation — A genetic alteration (lysine methyltransferase 2A translocation) required for therapy eligibility with Revuforj.

DefinitionKMT2A gene translocation — a lysine methyltransferase 2A (KMT2A) gene translocation; presence is required for Revuforj (Revumenib) therapy eligibility.

Indication linkageRevuforj is indicated for relapsed or refractory acute leukemia with a KMT2A translocation in adults and pediatric patients aged ≥1 year.

DocumentationPrior authorization requires documentation of KMT2A translocation as part of approval criteria.

inv-17: Clinical Policy — Clinical policy document

Document typeClinical Policy — this document is the Health Plan's clinical policy for Revumenib (Revuforj).

Proprietary statusThe clinical policy is the property of the Health Plan; unauthorized copying, use, or distribution is prohibited.

Contractual bindingProviders, members, and representatives are bound to the policy terms through contract or by providing services/submitting claims.

Step Therapy & Dose-Use Requirements

Step	Requirement	Notes / Dose limits
1
Member must use Revumenib (Revuforj) if available unless contraindicated or clinically significant adverse effects are experienced.
Dose must not exceed specified limits; weight ≥ 40 kg dosing guidance applies. Approval duration: 6 months for initial approvals.