Health Net ipilimumab (Yervoy) Coverage Update

Coverage Criteria

Initial Therapy - Melanoma

Covered when ALL of the following are met for melanoma

Melanoma initial: Member has a diagnosis of melanoma; disease meets one of the following: unresectable or metastatic OR resectable/limited resectable/lymph node positive; prescribed by or in consultation with an oncologist; age criteria met (≥12 years for unresectable/metastatic disease; ≥18 years for adjuvant treatment); prescribed regimen is an FDA-approved regimen or recommended by NCCN; dosing limits: unresectable/metastatic monotherapy dose does not exceed 3 mg/kg IV every 3 weeks for a maximum of 4 doses; adjuvant dosing 3 mg/kg IV every 3 weeks for 4 doses followed by 3 mg/kg every 12 weeks for up to 4 additional doses; may be used as single agent or in combination with nivolumab (Opdivo) or other specified combinations (off-label combinations require supporting evidence).

Prescribed regimen must be FDA-approved or recommended by NCCN.

Initial Therapy - Renal Cell Carcinoma

Covered when ALL of the following are met for RCC

RCC initial: Diagnosis of advanced or metastatic renal cell carcinoma; prescribed by or in consultation with an oncologist; age ≥12 years; prescribed in combination with nivolumab (Opdivo); dosing: ipilimumab dose does not exceed 1 mg/kg IV every 3 weeks for a maximum of 4 doses (or dose supported by practice guidelines/peer‑reviewed literature for off‑label use with supporting evidence); prescribed regimen must be FDA‑approved or recommended by NCCN.

Prior authorization may be required for combination agent (Opdivo).

Initial Therapy - Colorectal Cancer (MSI-H/dMMR)

Covered when ALL of the following are met for CRC

CRC initial: Diagnosis of colorectal cancer with MSI‑H or dMMR (or POLE mutation where specified); prescribed by or in consultation with an oncologist; age ≥12 years; disease is unresectable, metastatic, or advanced; prescribed in combination with nivolumab (Opdivo); dosing: ipilimumab dose does not exceed 1 mg/kg IV every 3 weeks in combination regimens for a maximum of 4 doses (or dose supported by practice guidelines/peer‑reviewed literature for off‑label use with supporting evidence); approval duration: 16 weeks (maximum of 4 doses).

Prescribed regimen must be FDA‑approved or recommended by NCCN.

Initial Therapy - Hepatocellular Carcinoma

Covered when ALL of the following are met for HCC

HCC initial: Diagnosis of hepatocellular carcinoma with disease that is unresectable, metastatic, or advanced; prescribed by or in consultation with an oncologist; age ≥18 years; prescribed in combination with nivolumab (Opdivo) as first‑line systemic therapy when ineligible for resection/transplant/locoregional therapy or as subsequent‑line systemic therapy provided member has not received prior anti‑CTLA‑4–based combinations; dosing: ipilimumab does not exceed 3 mg/kg IV every 3 weeks for a maximum of 4 doses (or dose supported by guidelines/peer‑reviewed literature for off‑label use with supporting evidence); approval duration: 16 weeks (maximum of 4 doses).

Prescribed regimen must be FDA‑approved or recommended by NCCN; prior requirements for Child‑Pugh Class A and specific prior therapies removed per updated criteria.

Initial Therapy - Non-Small Cell Lung Cancer

Covered when ALL of the following are met for NSCLC

NSCLC initial: Diagnosis of recurrent, advanced, or metastatic non‑small cell lung cancer; prescribed by or in consultation with an oncologist; age ≥18 years; member does not have contraindications to PD‑1/PD‑L1 inhibitors; prescribed in combination with nivolumab (Opdivo); disease mutation status criteria met where specified (e.g., absence of actionable biomarkers for some first‑line uses or prior therapy requirements for certain mutations); dosing: ipilimumab does not exceed 1 mg/kg IV every 6 weeks in combination with nivolumab; approval duration: 6 months.

Prescribed regimen must be FDA‑approved or recommended by NCCN.

Initial Therapy - Malignant Pleural Mesothelioma

Covered when ALL of the following are met for malignant pleural mesothelioma

Mesothelioma initial: Diagnosis of malignant pleural mesothelioma; prescribed by or in consultation with an oncologist; age >18 years; prescribed in combination with nivolumab (Opdivo); dosing: ipilimumab does not exceed 1 mg/kg IV every 6 weeks in combination with nivolumab (or dose supported by practice guidelines/peer‑reviewed literature for off‑label use with supporting evidence).

Prescribed regimen must be FDA‑approved or recommended by NCCN; prior authorization may be required for combination agent.

Initial Therapy - Esophageal Cancer

Covered when ALL of the following are met for esophageal squamous cell carcinoma

Esophageal cancer initial: Diagnosis of esophageal squamous cell carcinoma (ESCC) with disease that is unresectable advanced or metastatic AND tumor expresses PD‑L1 (Combined Positive Score [CPS] ≥1); prescribed by or in consultation with an oncologist; age >18 years; prescribed in combination with nivolumab (Opdivo); dosing: ipilimumab does not exceed 1 mg/kg IV every 6 weeks in combination with nivolumab (or dose supported by practice guidelines/peer‑reviewed literature for off‑label use with supporting evidence).PD-L1 positive

Prescribed regimen must be FDA‑approved or recommended by NCCN; PD‑L1 expression requirement added per updated approval.

Initial Therapy - NCCN Compendium Indications

Covered when ALL of the following are met for NCCN compendium indications (off-label)

NCCN compendium initial: Diagnosis of a tumor type listed in the NCCN compendium (examples include MSI‑H or dMMR tumors such as small bowel adenocarcinoma, ampullary adenocarcinoma, gastric cancer, esophageal adenocarcinoma; biliary tract cancers; selected sarcomas; uveal melanoma; Merkel cell carcinoma; gestational trophoblastic neoplasia; etc.); age ≥12 years; prescribed by or in consultation with an oncologist; prescribed as single agent or in combination with nivolumab for specified tumor types where indicated; dosing is within FDA maximum limit for any FDA‑approved indication or is supported by practice guidelines/peer‑reviewed literature for the off‑label use (prescriber must submit supporting evidence); approval duration: 6 months.

Prescribed regimen must be FDA‑approved or recommended by NCCN; prior authorization for Opdivo may be required.

NCCN Compendium Indications (off‑label)

Covered when ALL of the following are met for NCCN compendium (off‑label) indications:

NCCN off‑label approval requirements: 1) Member is currently receiving medication via Centene benefit or documentation supports current receipt of Yervoy for a covered indication and has received it for at least 30 days; 2) Member is responding positively to therapy; 3) Dose is within FDA maximum limit for any FDA‑approved indication or is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence).

Approval duration: 12 months

Selected updated coverage criteria

Coverage aligns with updated FDA-approved indications and prescribing information; select examples of revised criteria include:

HCC (with nivolumab): Use covered when disease is unresectable, metastatic or advanced and used in combination with nivolumab as first‑line therapy per FDA approval and prescribing information.

Removed prior requirements for Child‑Pugh Class A and prior specific therapies; converted accelerated approvals to full approvals.

ESCC (with nivolumab): Use covered in unresectable advanced or metastatic ESCC in combination with nivolumab only when tumor expresses PD‑L1, with options for induction, neoadjuvant, perioperative, or palliative intent as specified.PD-L1 positive

Indication limited to PD‑L1 expressing tumors per updated approval.

CRC (dMMR/MSI-H): Updated to allow earlier line of therapy per FDA approvals; dosing capped at a maximum of 4 doses per prescribing information.max 4 doses

If the requested use is not on the formulary/PDL or is not listed in this policy, follow the applicable plan-specific no-coverage or non-formulary policy for the member's line of business (for example, CP.CPA.190 for commercial, HIM.PA.33/HIM.PA.103 for marketplace, or CP.PMN.255/CP.PMN.16 for Medicaid). If the requested use is not specifically listed in section III and the above does not apply, refer to the applicable off‑label use policy for the line of business (for example, CP.CPA.09 for commercial, HIM.PA.154 for marketplace, or CP.PMN.53 for Medicaid).

Providers should submit the required clinical documentation to support medical necessity (see documentation and prior authorization sections). Failure to follow the formulary/non‑formulary or off‑label referral instructions may result in denial or referral to the line‑of‑business policy for coverage determination.

Non‑FDA approved indications that are not addressed in this policy are excluded from coverage unless the prescriber provides sufficient documentation of efficacy and safety as required by the applicable off‑label use policy for the member's line of business (for example, CP.CPA.09 for commercial, HIM.PA.154 for marketplace, or CP.PMN.53 for Medicaid).

For requests considered under the NCCN Compendium (off‑label) pathway, the prescriber must submit supporting evidence (guideline or peer‑reviewed literature) and required documentation described elsewhere in this policy; absent sufficient documentation, requests for off‑label uses may be denied.

Appendix D lists indications that NCCN and the policy authors no longer recommend for use of Yervoy. Those removed or ‘‘no longer recommended’’ indications are excluded from coverage under this policy.

Examples and lists of no‑longer‑recommended indications are detailed in Appendix D and Appendix B updates; providers should not expect coverage for these removed uses unless new evidence or guideline changes are adopted and the policy is updated.

Reauthorization beyond the initial approval durations specified for each indication is not permitted except where the policy explicitly provides continuation criteria. For example, reauthorization for unresectable or metastatic melanoma beyond the common induction period is prohibited: reauthorization beyond 16 weeks is not permitted unless the member meets the listed continuation criteria.

When continuation is allowed by indication, the member must meet the applicable renewal requirements (for example, documented ongoing clinical benefit and adherence to dosing limits); otherwise additional authorization will be denied.

NCCN has removed recommendations for Yervoy in several tumor types (see Appendix D). In addition, PD‑1/PD‑L1 inhibitors (and their combinations) may be contraindicated or provide less benefit in patients with certain oncogenic drivers or active autoimmune disease. Providers should review Appendix C/D guidance and contraindications when requesting therapy.

Coverage decisions reflect these NCCN updates: uses newly listed as ‘‘no longer recommended’’ are excluded from coverage and clinical scenarios with contraindications (for example active autoimmune disease or concurrent immunosuppression) may preclude approval.

Use of ipilimumab (Yervoy) outside of updated FDA‑approved indications or in ways that exceed prescribing information dosing limits is considered not medically necessary. Specifically, continuation or dosing that would exceed the prescribing information maximums (for example, dosing beyond a maximum of 4 doses where the PI specifies this limit) is not supported for coverage.

Initial Therapy Criteria

Initial Therapy — diagnosis-specific criteria, oncologist involvement, age, combination/regimen specs, dosing referenced

Initial approval requires diagnosis‑specific criteria, oncologist involvement, age requirements, combination/regimen specifications, and dosing limits:

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Initial therapy dosing

Dosing regimens referenced by indication

Melanoma dosing: Adjuvant: 3 mg/kg IV every 3 weeks up to 4 doses, followed by 3 mg/kg every 12 weeks for up to 4 additional doses. Unresectable/metastatic: monotherapy 3 mg/kg IV every 3 weeks for a maximum of 4 doses; in combination with nivolumab the regimen and doses follow PI guidance.

Maximum 3 mg/kg per dose for melanoma.

RCC and CRC dosing (combination): RCC: 1 mg/kg IV every 3 weeks with nivolumab 3 mg/kg for a maximum of 4 doses. CRC: 1 mg/kg IV every 3 weeks with nivolumab 3 mg/kg (for age ≥12 years and weight ≥40 kg) or nivolumab 240 mg for a maximum of 4 doses.

Continuation / Reauthorization Criteria

Continuation Therapy

Criteria for continuation/reauthorization vary by indication and are limited.

Continuation - Melanoma unresectable/metastatic: Reauthorization beyond 16 weeks is not permitted; members must meet initial approval criteria and be at least 3 months since initial treatment discontinuation.

Reauthorization beyond 16 weeks not permitted per policy.

Continuation - Melanoma adjuvant, NSCLC, Mesothelioma, ESCC: Member currently receiving Yervoy via Centene benefit or documentation of current therapy ≥30 days; member is responding positively to therapy; for melanoma adjuvant new dose does not exceed 3 mg/kg every 12 weeks for up to 4 additional doses; for NSCLC, mesothelioma, and ESCC new dose does not exceed 1 mg/kg IV every 6 weeks in combination with nivolumab; approval duration: up to 12 months or specified durations (e.g., up to 4 additional doses for cutaneous melanoma or up to 2 years for certain indications), whichever is less.

Dose increases require guideline or literature support.

Continuation - NCCN compendium:

Provider Actions and Prior Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required for ipilimumab (Yervoy). Providers must submit a prior authorization request and include documentation that the requested use meets the clinical indication criteria (diagnosis, prior therapies, dosing, combination regimens) per this policy.

HCPCS for billing: J9228 — Injection, ipilimumab; mg (informational only, verify current coding guidance)
Follow Health Net prior authorization submission processes and include clinical documentation as noted below

Note

Authorization Follows Current FDA / Clinical Guidance

When requesting authorization, reviewers will evaluate the request against the policy’s current FDA‑approved and NCCN-recommended indications (including any updated indication language such as PD‑L1 requirements for ESCC and updated line‑of‑therapy language for CRC and HCC). Requests inconsistent with current FDA indications or the policy’s dosing limits (e.g., exceeding the maximum of 4 induction doses where applicable) may be denied.

Authorization decisions follow updated FDA labeling and relevant companion diagnostic requirements (for example, PD‑L1 CPS ≥1 where specified)

Coding and Quantity Limits

HCPCS CodesHCPCS

J9228

Injection, ipilimumab; mg

Maximum induction doses

Maximum induction dosesMaximum of 4 doses commonly referenced across multiple indications (melanoma, RCC, CRC, HCC, NSCLC, mesothelioma, ESCC).

Melanoma dosing capAdjuvant and unresectable/metastatic melanoma dosing limited to a maximum of 4 induction doses (3 mg/kg every 3 weeks for up to 4 doses).

Combination regimensWhen used in combination with nivolumab for RCC/CRC/NSCLC/mesothelioma/ESCC, ipilimumab dosing is typically limited to regimens that specify a maximum of 4 induction doses (e.g., 1 mg/kg every 3 weeks or every 6 weeks as indicated).

Policy alignmentCoverage and continuation decisions follow FDA prescribing information and PI dosing limits which specify a maximum of 4 doses for many indications.

Step Therapy

Step therapy summary	Policy detail / provider requirement
No explicit step-therapy algorithm stated	Policy does not mandate a required sequence of prior agents before ipilimumab; many indication-specific approvals require ipilimumab to be prescribed as a single agent or in combination with nivolumab (Opdivo) per FDA or NCCN recommendations. Prescriber must document regimen rationale and relevant indication-specific criteria (diagnosis, age, regimen, dosing limits).

Step therapy summary	Policy detail / provider requirement
Incorporates NCCN guidance and review of prior therapies/mutation status for select indications	For certain indications (for example NSCLC), the policy incorporates NCCN guidance and requires review of prior therapies and tumor mutation status as part of the approval decision. Documentation of mutation status or lack of actionable mutations and prior therapy history should be provided when requested. Unknown mutation status is no longer allowed for specified indications per NCCN updates.

Step therapy summary	Policy detail / provider requirement
No specific sequencing; coverage follows updated FDA indications and PI	The policy does not define a formal step‑therapy sequence; coverage and prior‑authorization decisions are aligned to updated FDA‑approved indications and prescribing information (including dosing limits and indication‑specific requirements such as PD‑L1 status for ESCC). Providers must document indication and dosing consistent with the PI.

Quantity Limits

Ipilimumab (Yervoy) — maximum of 4 doses

Drug and brandIpilimumab (Yervoy).

Maximum doses per courseMaximum of 4 doses for commonly referenced induction regimens (per prescribing information).

Typical dosing examplesMelanoma: 3 mg/kg IV every 3 weeks for up to 4 doses; RCC/CRC combinations: 1 mg/kg every 3 weeks for up to 4 doses.

Reference for billing/codingHCPCS code J9228 used for ipilimumab (see policy coding section).

Site of Care

Note

Site of care — not specified in this excerpt

Site‑of‑care is not specified in this excerpt of the policy; follow standard Health Plan site‑of‑care policies for infusion services.

No specific site‑of‑care restriction appears in this section; use usual infusion center workflows and billing practices.
Refer to plan policies if a site‑of‑care limitation is necessary for a specific line of business.

Note

No site‑of‑care restriction specified in this section

This section does not impose a site‑of‑care restriction; providers should follow their line‑of‑business policies for infusion location and reimbursement.

Use standard infusion center billing and documentation procedures unless otherwise directed by the Health Plan.
Check line‑of‑business guidance for any outside restrictions.

Note

No site‑of‑care restrictions specified — follow standard plan policies

Background

Ipilimumab (Yervoy) is a human monoclonal antibody that blocks cytotoxic T‑lymphocyte antigen‑4 (CTLA‑4), an immune checkpoint receptor. It is indicated in multiple malignancies and is commonly used as a single agent or in combination with nivolumab (Opdivo) depending on the tumor type and FDA/NCCN guidance.

This policy aligns coverage with updated FDA approvals and NCCN compendium recommendations; where the FDA label or NCCN guidance has been revised (for example, PD‑L1 requirement for ESCC or first‑line combination use in HCC), authorization decisions will reflect those updates.

Definitions

CTLA-4-blocking antibody — Ipilimumab (Yervoy)

Class descriptionCTLA-4-blocking antibody: ipilimumab (Yervoy) is a human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking monoclonal antibody.

Mechanism termCTLA-4 stands for cytotoxic T-lymphocyte antigen 4; see abbreviations.

Clinical roleUsed as an immune checkpoint inhibitor across multiple malignancies, alone or in combination with nivolumab.

cytotoxic T-lymphocyte antigen 4 (CTLA-4)

TermCytotoxic T-lymphocyte antigen 4 (CTLA-4).

AbbreviationCTLA-4 is listed in the policy abbreviation key.

Relevance

OpenPayer

Clinical Policy: Ipilimumab (Yervoy)

Coverage Criteria

Initial Therapy Criteria

Continuation / Reauthorization Criteria

Provider Actions and Prior Authorization

Coding and Quantity Limits

Step Therapy

Quantity Limits

Site of Care

Background

Definitions