Centene Hepzato Coverage Update: Prior Auth

Coverage and Medical Necessity Criteria

inv-01: Initial Therapy

Covered when ALL of the following are met for Uveal Melanoma (Initial Approval):

Uveal Melanoma Initial Criteria: 1. Diagnosis of unresectable or metastatic uveal melanoma; 2. Prescribed by or in consultation with an oncologist; 3. Age ≥ 18 years; 4. Weight ≥ 35 kg; 5. Histologically or cytologically-proven ocular melanoma metastases affecting 50% or less of the parenchyma of the liver; 6. Either (a) no extrahepatic disease or (b) extrahepatic disease limited to bone, lymph nodes, subcutaneous tissues, or lung that is amenable to resection or radiation; 7. Recent (within the last 30 days) hematologic testing demonstrating: (a) platelet count ≥100,000/µL, (b) hemoglobin ≥10 g/dL, and (c) neutrophils >2,000/µL; 8. No Child-Pugh Class B or C cirrhosis; 9. Requested dose meets one of the following: (a) does not exceed both (i) 3 mg/kg based on ideal body weight every 6 weeks (up to 6 total infusions) and (ii) 220 mg per infusion, or (b) dose is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence).

Approval duration: 12 months

inv-02: Continuation Therapy

Continued therapy (must meet all):

Uveal Melanoma Continued Therapy: 1. Currently receiving medication via Centene benefit, or documentation supports member is currently receiving Hepzato for a covered indication and has received the medication for at least 30 days; 2. Member is responding positively to therapy; 3. Member has not received ≥ 6 total Hepzato infusions; 4. If request is for a dose increase, new dose must either (a) not exceed both (i) 3 mg/kg based on ideal body weight every 6 weeks (up to 6 total infusions) and (ii) 220 mg per infusion, or (b) be supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence).

Approval duration: 12 months (up to 6 total infusions)

inv-03: Other Indications / Off‑label Process

Other Diagnoses/Indications: 1. If the drug has recently undergone a label change within the last 6 months that is not yet reflected in this policy, follow the formulary/no-coverage or non‑formulary policy for the relevant line of business as specified; 2. If the requested use is not listed under section III (Diagnoses/Indications for which coverage is NOT authorized) and criterion 1 does not apply, refer to the applicable off‑label use policy for the relevant line of business (commercial, health insurance marketplace, or Medicaid).

Requests for uses that are non‑FDA approved indications not addressed in this policy are excluded unless the provider submits sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policies: CP.CPA.09 (Commercial), HIM.PA.154 (Health Insurance Marketplace), or CP.PMN.53 (Medicaid), or unless coverage is established in the member’s evidence of coverage document.

Within the provided policy text there are no explicit clinical exclusions listed beyond those addressed elsewhere in this document. Where state Medicaid requirements conflict with this clinical policy, Medicaid provisions take precedence and the applicable state policy or evidence of coverage governs.

Use is considered Not Medically Necessary (NMN) when a requested non‑FDA indication lacks adequate evidence per the off‑label use policies referenced above or when a contraindication is present (for example: active intracranial metastases, liver failure or portal hypertension, recent liver surgery, uncorrectable coagulopathy, inability to safely undergo general anesthesia, or severe hypersensitivity to melphalan or Hepzato components). In such cases the request will be denied unless supporting evidence meeting the off‑label criteria is provided.

The document excerpts provided do not list any additional, specific conditions that are explicitly categorized as Not Medically Necessary beyond the general statements about off‑label use and contraindications; standard medical necessity adjudication and the coverage document terms apply.

Billing and Coding

HCPCS CodesHCPCS

J9248

Injection, melphalan (hepzato), 1 mg

HCPCS CodesHCPCS

J9248

Injection, melphalan (hepzato), 1 mg

Maximum infusions

Maximum infusionsUp to 6 total infusions

Treatment intervalEvery 6 to 8 weeks (may be delayed for toxicity recovery)

Approval duration12 months

Dosing limits

Recommended dose3 mg/kg based on ideal body weight (IBW) every 6 weeks

Maximum per infusion220 mg per infusion

Dosing justification

Provider Requirements and Prior Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required for Hepzato (HCPCS J9248). Approval will be granted only when all policy clinical criteria and documentation requirements are met.

Prior authorization required for Hepzato (Injection, melphalan (hepzato), 1 mg) — HCPCS J9248.
Approval contingent on meeting all clinical criteria in this policy (see Initial Approval Criteria and Appendix C).

Denial Risk

Non‑FDA Indications

Requests for non‑FDA (off‑label) indications that are not specifically addressed in this policy will be denied unless the prescriber provides sufficient supporting evidence of efficacy and safety in accordance with the applicable off‑label use policies.

Non‑FDA uses not listed in this policy require submission of supporting evidence (peer‑reviewed literature or guideline support).

Background and Drug Information

Hepzato (melphalan for hepatic delivery) is a liver‑directed alkylating agent formulated for intra‑arterial infusion into the hepatic artery and is indicated for adult patients with uveal melanoma with unresectable hepatic metastases that involve less than 50% of the liver parenchyma and have limited or no extrahepatic disease. Treatment is administered in an infusion setting via hepatic intra‑arterial infusion and is associated with risks including myelosuppression and peri‑procedural complications.

Definitions and Key Terms

Hepzato — product description

Generic name / formulationMelphalan for hepatic delivery (Hepzato)

Mechanism / classAlkylating agent formulated for intra‑arterial hepatic infusion

Indication summaryLiver‑directed treatment for adult patients with uveal melanoma with unresectable hepatic metastases affecting <50% of the liver; limited extrahepatic disease may be eligible

Ideal body weight (IBW) — dosing basis and formulas

IBW basis for dosingDosing calculations use ideal body weight (IBW); recommended dose is 3 mg/kg IBW

IBW formula — height ≥ 152 cmIBW = 52 kg + (0.75 kg × height(cm) above 152 cm) [alternative formula in document: 49 kg + (0.67 kg/cm above 152 cm) appears in dosing section]

Initial Therapy Specific Criteria

inv-25: Initial Therapy

Initial therapy criteria for uveal melanoma

Initial Therapy: See coverage criteria: diagnosis of unresectable or metastatic uveal melanoma; prescribed by or in consultation with an oncologist; age ≥18 years; weight ≥35 kg; histologically or cytologically-proven ocular melanoma metastases affecting ≤50% of liver parenchyma; no extrahepatic disease OR extrahepatic disease limited to bone, lymph nodes, subcutaneous tissues, or lung amenable to resection or radiation; recent (within 30 days) labs meeting platelet ≥100,000/µL, hemoglobin ≥10 g/dL, neutrophils >2,000/µL; no Child‑Pugh Class B or C; dosing within 3 mg/kg IBW every 6 weeks and ≤220 mg per infusion or supported by guidelines/literature (prescriber evidence required).

Approval duration: 12 months

Criteria for Continued Therapy and Approval Duration

inv-27: Continuation

Continued therapy requirements

Continued Therapy: Member has been on therapy ≥30 days via Centene benefit or documentation supports current Hepzato use; member is responding to therapy; total infusions <6; dosing remains within policy limits (3 mg/kg IBW every 6 weeks and ≤220 mg per infusion) or any dose increase is supported by practice guidelines or peer‑reviewed literature with prescriber evidence.

Approval duration: 12 months (up to 6 total infusions)

inv-28: Approval duration

Initial approval duration for maintenance therapy was extended.

Initial approval duration change: Initial approval duration extended from 6 months to 12 months for this maintenance medication for a chronic condition.

Applied during 4Q 2025 annual review.

Step Therapy and Prior Routing

Step	Requirement / Routing
1	For requested uses not listed in this policy: follow formulary/no‑coverage or non‑formulary policy routing based on the drug's formulary/PDL status and the member's line of business (see CP.CPA.190, HIM.PA.33, CP.PMN.255 for formulary/no‑coverage; or CP.CPA.190, HIM.PA.103, CP.PMN.16 for non‑formulary). If the use is not addressed by those rules and the label change condition does not apply, refer to the off‑label use policy for the relevant line of business (CP.CPA.09, HIM.PA.154, CP.PMN.53).

Step

Requirement / Routing

For requested uses not listed in this policy: follow formulary/no‑coverage or non‑formulary policy routing based on the drug's formulary/PDL status and the member's line of business (see CP.CPA.190, HIM.PA.33, CP.PMN.255 for formulary/no‑coverage; or CP.CPA.190, HIM.PA.103, CP.PMN.16 for non‑formulary). If the use is not addressed by those rules and the label change condition does not apply, refer to the off‑label use policy for the relevant line of business (CP.CPA.09, HIM.PA.154, CP.PMN.53).

Product Presentation and Quantity Limits

Hepzato (melphalan) — product presentation

Presentation per vial50 mg lyophilized powder per vial

Package configurationPackaged as 5 single‑dose vials

Product formInjection — lyophilized powder for reconstitution for intra‑arterial hepatic infusion

Administration and Site of Care

Note

Administer via intra‑arterial hepatic infusion in infusion center/IR

Administer Hepzato by intra‑arterial infusion into the hepatic artery with a 30‑minute infusion followed by a 30‑minute washout; treatments are given every 6 to 8 weeks (can be delayed for toxicity recovery) and are delivered in an infusion center/interventional radiology setting.

Dosing regimen: 3 mg/kg based on ideal body weight; maximum 220 mg per treatment; up to 6 total infusions.

Policy Revision History

08.01.24code_added

HCPCS code J9248 (injection, melphalan (Hepzato), 1 mg) was added to the coding table during the 4Q 2024 annual review.

07.17.25approval_duration_extendedLatest

Initial approval duration was extended from 6 months to 12 months for this maintenance medication (applied during the 4Q 2025 annual review).

OpenPayer

Melphalan for Hepatic Delivery (Hepzato)