ModifiedCentenePolicy CP PHAR.542

Talimogene laherepvec (Imlygic) therapy

Coverage and medical necessity criteria for talimogene laherepvec (Imlygic) for treatment of unresectable cutaneous, subcutaneous, and nodal melanoma lesions and selected off-label uses; applies to members under Centene-affiliated health plans.

Policy Summary

PayerCentene

PolicyTalimogene laherepvec (Imlygic) therapy

Policy CodePolicy CP PHAR.542

Change TypeMaterial revisions (added off-label Merkel cell carcinomadosing and documentation clarifications)

Effective Date09.01.21

Next Review Date

Key ActionSubmit prior authorization with documentation of lesion type, quantity, and sizes and reference J9325 for billing.

SourceLink

POLICY UPDATE CHANGES

Added off-label criteria for Merkel cell carcinoma per NCCN.

Added criteria for metastatic melanoma and off-label combination use with Yervoy; clarified documentation required in continued therapy to include type, quantity, and size of new or remaining lesions.

Updated dosing in initial approval criteria to include both initial and subsequent dosing and reinitiation dose aligned with prescribing information.

6 moinitial approval duration

12 mocontinued therapy duration

J9325HCPCS code

106 & 108 PFU/mL

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Coverage and Medical Necessity Criteria

Initial Approval - Melanoma

Covered when ALL of the following are met

Initial melanoma criteria: 1. Diagnosis of unresectable, limited resectable, or metastatic melanoma; 2. Prescribed by or in consultation with an oncologist; 3. Age ≥ 18 years; 4. Prescribed as a single agent OR in combination with Yervoy as subsequent therapy for metastatic or unresectable melanoma (off-label) (prior authorization for Yervoy may be required); 5. Documentation that lesions are cutaneous, subcutaneous, or nodal and documentation of quantity and sizes of lesions; 6. Request meets one of the following dosing conditions: (a) Initial dose does not exceed 4 mL of 10^6 PFU/mL; (b) For all subsequent doses (starting 3 weeks after the initial dose) and for reinitiation, dose does not exceed 4 mL of 10^8 PFU/mL every 2 weeks; OR dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA‑approved or recommended by NCCN.

Approval duration: 6 months

Initial Approval - Merkel Cell Carcinoma (off-label)

Covered when ALL of the following are met

Merkel cell carcinoma criteria: 1. Diagnosis of Merkel cell carcinoma; 2. Prescribed by or in consultation with an oncologist; 3. Age ≥ 18 years; 4. Prescribed as a single agent when curative surgery or radiation therapy is not feasible; 5. Disease is metastatic; 6. Lesions are cutaneous, subcutaneous, or nodal with documentation of quantity and sizes of lesions; 7. Request meets one of the following dosing conditions: (a) Initial dose does not exceed 4 mL of 10^6 PFU/mL; (b) For all subsequent doses (starting 3 weeks after the initial dose) and for reinitiation, dose does not exceed 4 mL of 10^8 PFU/mL every 2 weeks; OR dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA‑approved or recommended by NCCN.

Approval duration: 6 months

Continued Therapy

Covered when ALL of the following are met

Continued therapy criteria: 1. Member is currently receiving Imlygic via Centene benefit, or documentation supports that member is currently receiving Imlygic for a covered indication and has received the medication for at least 30 days; 2. Member is responding positively to therapy; 3. New or remaining lesions are cutaneous, subcutaneous, or nodal; 4. Documentation of quantity and sizes of new or remaining lesions; 5. If request is for a dose increase, the new dose must be supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA‑approved or recommended by NCCN.

Approval duration: 12 months

Requests for uses that are not FDA‑approved and are not specifically addressed in this policy are excluded unless the provider submits sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policy for the member's line of business. Refer to the off‑label policies: CP.CPA.09 (commercial), HIM.PA.154 (health insurance marketplace), and CP.PMN.53 (Medicaid). For drugs that are on or off the formulary/PDL, follow the referenced no coverage or non‑formulary policies as applicable per the guidance in this policy.

When state Medicaid coverage provisions conflict with this clinical policy, state Medicaid provisions take precedence. Providers should consult the applicable state Medicaid manual for any specific coverage rules that supersede the policy.

Imlygic is not authorized for treatment of visceral metastases and has not been shown to improve overall survival or affect visceral disease; use for visceral metastases is therefore not covered. Additionally, non‑FDA indications that lack sufficient supporting evidence and are not permitted by the applicable off‑label policies will be denied.

Initial Therapy Dosing and Authorization

Initial therapy dosing

Initial dosing and authorization requirements

Initial dosing: Recommended starting regimen: Initial injection up to 4 mL at 10^6 (1 million) PFU/mL; followed by up to 4 mL of 10^8 (100 million) PFU/mL administered 3 weeks later; thereafter, subsequent doses (including reinitiation) up to 4 mL of 10^8 PFU/mL every 2 weeks. Injection volume per lesion should follow the lesion‑size guidance in Appendix D (table for determination of injection volume).

Criteria for Continued Coverage

Continued therapy

Criteria for continued coverage

Continued therapy nodes: 1. Member must have ≥ 30 days of prior Imlygic therapy via Centene benefit or documentation of current therapy for a covered indication; 2. Member must be responding positively to therapy; 3. New or remaining lesions must be cutaneous, subcutaneous, or nodal with documentation of type, quantity, and sizes of lesions; 4. If request includes a dose increase, the new dose must be supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA‑approved or recommended by NCCN.

Billing Codes and Injection Details

HCPCS CodesHCPCS

J9325

Injection, talimogene laherparepvec, per 1 million plaque forming units

inv-08: Maximum injection volume per treatment — up to 4 mL at 108 PFU/mL (all lesions combined)

Maximum injection volume per treatmentUp to 4 mL total per treatment (all lesions combined) at a concentration of 10^8 PFU/mL

Initial injection concentrationRecommended starting dose: up to 4 mL at 10^6 PFU/mL

Subsequent/reinitiation dosingAfter initial dose, up to 4 mL of 10^8 PFU/mL administered 3 weeks later; then up to 4 mL of 10^8 PFU/mL every 2 weeks

Prior Authorization, Documentation, and Provider Responsibilities

Prior Authorization

Prior Authorization Required

Prior authorization is required for requests as indicated by the plan. Providers should obtain prior authorization when submitting requests for talimogene laherparepvec (Imlygic).

Prior authorization required (contact Health Plan for submission details)
HCPCS: J9325 referenced for billing guidance (informational only)

Denial Risk

Denial Risk and Coverage Limits

Coverage decisions are subject to the Health Plan's terms, conditions, exclusions, limitations, and applicable state and federal requirements. Requests that do not meet policy criteria, that are for non‑FDA indications not supported per the plan's off‑label use policies, or that conflict with regulatory requirements may be denied.

Denial triggers include: failure to meet listed policy criteria, requests for indications not supported by FDA or referenced off‑label policy, and noncompliance with regulatory or contractual requirements

Combination and Step Therapy Notes

Scenario	Requirement	Coverage label
Imlygic prescribed as single agent for unresectable, limited resectable, or metastatic melanoma	Diagnosis of unresectable, limited resectable, or metastatic melanoma; prescribed by or in consultation with an oncologist; age ≥ 18 years; lesions are cutaneous, subcutaneous, or nodal with documentation of quantity and sizes; dosing meets initial dose ≤ 4 mL of 106 PFU/mL or subsequent/reinitiation doses ≤ 4 mL of 108 PFU/mL every 2 weeks (or dose supported by practice guidelines/peer‑reviewed literature); prescribed regimen must be FDA‑approved or NCCN‑recommended; approval duration: 6 months	Coverage for Imlygic as single agent
Imlygic used in combination with Yervoy as subsequent therapy for metastatic or unresectable melanoma	All initial approval criteria as above apply; prior authorization for Yervoy may be required when used in combination; prescribed regimen must be FDA‑approved or NCCN‑recommended; approval duration: 6 months	Prior authorization may be required for Yervoy when used in combination

Quantity and Vial Concentrations

inv-22: Imlygic — up to 4 mL

Quantity limit per treatmentImlygic: up to 4 mL per treatment

Available concentrations10^6 PFU/mL (initial) and 10^8 PFU/mL (subsequent)

Injection volume guidancePer lesion injection volumes determined by lesion size table (Appendix D); clustered lesions injected together as a single lesion

Administration Setting

Note

Administer as local injection in office or infusion center per dosing guidance

Imlygic is administered by local injection into cutaneous, subcutaneous, and/or nodal lesions per the dosing guidance in the policy; site of care includes office or infusion center.

Injection volumes and concentrations must follow the dosing table (e.g., up to 4 mL at specified PFU/mL).
Approved settings: office or infusion center.

Clinical Background

Talimogene laherparepvec (Imlygic) is a genetically modified oncolytic viral therapy indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery. Limitation: Imlygic has not been shown to improve overall survival or have an effect on visceral metastases.

Key Terms and Units

inv-18: plaque-forming units — PFU definition/usage

DefinitionPFU = plaque-forming units (unit used to quantify viable virus particles)

Usage in dosingImlygic dosing expressed in PFU per mL: initial dose often 10^6 PFU/mL; subsequent doses 10^8 PFU/mL

Billing relevanceHCPCS billing (J9325) references dosing per 1 million PFU for administration reporting

Policy Revisions and Review History

2023-05-09annual_review

Updated dosing in initial approval criteria to include both initial and subsequent dosing and added reinitiation dose to align with prescriber information; references reviewed and updated.

2024-05-23annual_review

Added criteria for metastatic melanoma and off-label combination use with Yervoy per NCCN; clarified continued therapy documentation to require type, quantity, and size of new or remaining lesions; references reviewed and updated.

2025-05-13annual_reviewLatest