ModifiedmhnPolicy CP.PHAR.629

Retifanlimab-dlwr (Zynyz) coverage

Defines medical necessity criteria, dosing, and authorization rules for retifanlimab-dlwr (Zynyz) for specified oncologic indications for members covered by the payer.

Policy Summary

Payermhn

PolicyRetifanlimab-dlwr (Zynyz) coverage

Policy CodePolicy CP.PHAR.629

Change TypeIndication additionscoding update

Effective DateJun 1, 2023

Next Review DateN/A

Key ActionSubmit prior authorization with documentation of diagnosis, prescriber specialty, age ≥18, and regimen/dosing (≤500 mg every 4 weeks) to support medical necessity.

SourceLink

POLICY UPDATE CHANGES

Added criteria for small bowel adenocarcinoma, colon cancer, and rectal cancer per NCCN 2A recommendation; for anal carcinoma, added option to be prescribed in combination with carboplatin and paclitaxel.

Added new FDA-approved indication for squamous cell carcinoma of the anal canal (SCAC).

Added Zynyz HCPCS code (J9345) and removed inactive codes.

Added pathways for primary locally advanced disease and recurrent regional disease for Merkel cell carcinoma (MCC) per NCCN 2A recommendation and required Zynyz be prescribed as a single agent.

500 mgStandard dose per administration

4 weeksDosing interval

J9345HCPCS code

6 monthsInitial approval duration

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Coverage Criteria

Continuation Therapy

For continuation of therapy, ALL of the following must be met

Continuation Criteria: 1. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Zynyz for a covered indication and has received this medication for at least 30 days. 2. Member is responding positively to therapy. 3. If request is for a dose increase, request meets one of the following: a. New dose does not exceed 500 mg (1 vial) every 4 weeks; b. New 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

Indication updates and approvals

Policy includes indication-specific criteria updated per NCCN 2A recommendations and new FDA approvals.

Updated Indications: Added pathways for primary locally advanced disease and recurrent regional disease for Merkel cell carcinoma per NCCN 2A; added criteria for anal carcinoma per NCCN 2A with later option to prescribe in combination with carboplatin and paclitaxel; added criteria for small bowel adenocarcinoma, colon cancer, and rectal cancer per NCCN 2A; added new FDA-approved indication for squamous cell carcinoma of the anal canal (SCAC).

Full eligibility criteria text and detailed node logic are documented in the indication-specific sections of this policy.

Non‑FDA approved indications that are not specifically addressed in this policy are not authorized unless the provider submits sufficient documentation of efficacy and safety consistent with the applicable off‑label use policies (CP.CPA.09 for commercial, HIM.PA.154 for the Health Insurance Marketplace, and CP.PMN.53 for Medicaid) or evidence of coverage that supports use.

Coverage under this clinical policy is subject to the member’s contract, evidence of coverage, and all Health Plan terms, conditions, exclusions, and limitations. The Health Plan’s administrative policies and procedures and any applicable state or federal requirements govern how this policy is applied and enforced.

Requests for retifanlimab‑dlwr (Zynyz) for indications that are not listed in Section I of this policy will be considered not authorized unless the prescriber provides adequate supporting documentation consistent with the referenced off‑label use policies or other evidence of coverage that justifies the requested use.

This portion of the policy does not list additional explicit "not medically necessary" conditions beyond the stipulations already described; coverage determinations remain subject to the member’s contract, plan exclusions, limitations, and applicable legal/regulatory requirements.

Coding

HCPCS CodesHCPCS

J9345

Injection, retifalimab-dlwr, 1 mg

Updated HCPCSHCPCS

Zynyz HCPCS code (unspecified)

Zynyz HCPCS code added per policy; exact HCPCS code number not provided in this window

Removed/Inactivated codesmixed

inactive codes (removed)

Policy removed inactive codes; specific codes not listed in this window

Maximum single dose — 500 mg

Maximum single dose500 mg IV per infusion (maximum dose specified for MCC and SCAC)

Dosing intervalEvery 4 weeks

Applies toMerkel cell carcinoma (MCC) and squamous cell carcinoma of the anal canal (SCAC)

Provider Actions & Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Requests must follow the Health Plan's prior authorization process and include clinical justification that the member meets the policy criteria (diagnosis, prescriber specialty, age, regimen details, and dosing). Be aware that Zynyz has an assigned HCPCS code; inactive codes were removed per the latest coding update.

PA required with documentation: diagnosis, prescriber specialty, age ≥18, regimen details
Zynyz HCPCS code added; inactive codes removed
Prior authorization applies per Health Plan processes and administrative requirements

Documentation Required

Provider must submit supporting documentation (office notes, lab results, pathology reports, prior treatment history, dosing rationale, and any guideline or literature supporting off‑label regimens). Failure to submit required documentation may result in denial or delay of the authorization request.

Background

Retifanlimab‑dlwr (Zynyz) is a programmed cell death‑1 (PD‑1) blocking monoclonal antibody used in oncology. It is indicated for certain advanced or recurrent malignancies, including metastatic or locally recurrent squamous cell carcinoma of the anal canal (SCAC) and Merkel cell carcinoma (MCC). Dosing in the policy is specified as 500 mg IV every 4 weeks, and some MCC indications are based on accelerated approval pending confirmatory trials. The policy aligns initiation and continuation criteria with NCCN recommendations and recent FDA approvals for SCAC and includes updated indication pathways for selected gastrointestinal cancers per NCCN 2A recommendations.

Definitions & Abbreviations

Abbreviations — MCC, SCAC and brief definitions

MCCMerkel cell carcinoma; aggressive skin cancer (policy references MCC dosing and indication)

SCACSquamous cell carcinoma of the anal canal; FDA‑approved indication for Zynyz in specified settings

PD‑1Programmed cell death protein 1 (class of agent; retifanlimab‑dlwr is a PD‑1 inhibitor)

Health Plan — definition/reference to Health Plan term

Health PlanThe payer or plan administering benefits; policy decisions are subject to the member's coverage documents and applicable Health Plan-level administrative policies

Medicaid precedenceFor Medicaid members, state Medicaid coverage provisions take precedence over this clinical policy when conflicts exist.

Initial Therapy Criteria

Initial Therapy

Indication-specific initial approval criteria (see each indication for required elements).

Initial Indications: See indication-specific initial criteria: Merkel cell carcinoma (MCC), squamous cell carcinoma of the anal canal (SCAC), and small bowel/colon/rectal cancers with qualifying molecular features (MSI-H, dMMR, or POLE/POLD1 ultra-hypermutated).

Refer to each indication's criteria for prescriber specialty, age requirement (â≥ 18 years), agent usage (single agent vs combination), and dosing limits (maximum 500 mg every 4 weeks or guideline-supported doses).

Continuation Criteria

Continuation Therapy

Continuation therapy requirements and monitoring

Continuation Therapy Monitoring: 1. Member has received Zynyz via the benefit for at least 30 days or documentation supports current therapy. 2. Clinical documentation demonstrates a positive response to therapy (e.g., physician assessment, imaging, or other objective measures). 3. Dose escalation requests must meet one of the following: a. New dose does not exceed 500 mg (1 vial) every 4 weeks; b. New dose is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence). 4. Provider must submit documentation (office notes, labs, imaging) supporting continued benefit; failure to submit adequate documentation may result in denial. 5. Continuation approvals follow the plan-specific approval durations (see policy for durations by line of business).

Continued use must align with FDA/NCCN-recommended regimens and plan administrative requirements.

Step Therapy

Indication	Step requirement	Notes
First-line squamous cell carcinoma of the anal canal (SCAC)	Zynyz may be used in combination with carboplatin and paclitaxel	Per updated criteria; no prior PD‑1 therapy step specified
Merkel cell carcinoma (MCC)	Zynyz required to be prescribed as a single agent	Requirement added in 2Q 2024 annual review (NCCN 2A); dose limitations still apply (≤500 mg every 4 weeks or supported by guidelines)

Indication	Required agent/regimen	Effective update / timing
Merkel cell carcinoma (MCC)	Zynyz as a single‑agent regimen	Specified as required in the 2Q 2024 annual review (NCCN 2A)
Squamous cell carcinoma of the anal canal (SCAC)	Zynyz as single agent or in combination with carboplatin and paclitaxel (combination option added)	Combination option permitted per 2Q 2025 annual review; SCAC later received FDA approval (RT4) per document timeline

Quantity Limits

retifanlimab-dlwr (Zynyz) — quantity limit / dose key value (500 mg)

Maximum per dose500 mg per single‑dose vial (500 mg/20 mL) — standard container size

Dosing per infusion500 mg IV infusion every 4 weeks

Unit descriptionSingle‑dose vial: 500 mg/20 mL (25 mg/mL)

Site of Care

Billing Rule

IV infusion at 500 mg every 4 weeks

Zynyz is administered by IV infusion. The policy specifies dosing of 500 mg given as an IV infusion every 4 weeks (maximum single dose 500 mg per infusion).

Dose and schedule: 500 mg IV every 4 weeks.
Administration setting: infusion center (IV infusion).