Blue Cross Blue Shield Iowa Yervoy Coverage Update

Coverage Criteria

Initial Approval — Cutaneous Melanoma

Authorization of 6 months may be granted for treatment of cutaneous melanoma when ALL of the following apply:

Cutaneous Melanoma - dosing and sequencing: Requested medication used as a single agent (for up to 4 doses) or in combination with nivolumab (for 4 doses followed by nivolumab as a single agent) for metastatic or unresectable disease; OR used as a single agent (for up to 8 doses) or in combination with nivolumab (for 4 doses followed by nivolumab as a single agent) as adjuvant treatment if no evidence of disease following systemic or metastasis-directed therapy (e.g., complete resection); OR used at low dose in combination with pembrolizumab for disease progression following anti-PD-1 therapy as subsequent therapy for metastatic or unresectable disease; OR used as a single agent (for up to 8 doses) for resectable disease after prior anti-PD-1 therapy; OR used in combination with nivolumab (for 4 doses followed by nivolumab as a single agent) as neoadjuvant treatment.dose and sequencing limits described

Preserve dosing limits and combination sequencing as stated; do not flatten.

Initial Approval — Uveal Melanoma

Authorization of 6 months may be granted for uveal melanoma when ANY of the following apply:

Uveal melanoma: Requested medication used as a single agent or in combination with nivolumab (for 4 doses followed by nivolumab as a single agent) for unresectable or metastatic disease.

6 month authorization duration.

Initial Approval — Gestational Trophoblastic Neoplasia

Authorization of 6 months may be granted for gestational trophoblastic neoplasia when ALL of the following are met:

Gestational trophoblastic neoplasia: Used in combination with nivolumab for multiagent chemotherapy-resistant disease when either (1) member has recurrent or progressive intermediate trophoblastic tumor (placental site trophoblastic tumor or epithelioid trophoblastic tumor) OR (2) member has high-risk disease.

6 month authorization.

Initial Approval — CNS Brain Metastases

Authorization of 6 months may be granted for CNS brain metastases when ALL of the following apply:

CNS brain metastases: Used as a single agent or in combination with nivolumab (for 4 doses followed by nivolumab as a single agent) for treatment of CNS brain metastases in members with melanoma.

6 month authorization.

Initial Approval — Non-Small Cell Lung Cancer

Authorization of 6 months may be granted for NSCLC when ALL of the following apply:

NSCLC: No EGFR exon 19 deletions or exon 21 L858R mutations and no ALK, RET, or ROS1 rearrangements (unless testing is not feasible due to insufficient tissue) AND requested medication will be used in a regimen containing nivolumab.molecular testing as described

6 month authorization.

Initial Approval — Renal Cell Carcinoma

Authorization of 6 months may be granted for renal cell carcinoma when ALL of the following apply:

Renal Cell Carcinoma: Used in combination with nivolumab (for 4 doses followed by single-agent nivolumab) for relapsed, advanced, or stage IV disease with clear cell histology.clear cell histology

6 month authorization.

Initial Approval — Colorectal Cancer

Authorization of 6 months may be granted for colorectal cancer when ALL of the following apply:

Colorectal Cancer: Tumor is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) OR has POLE/POLD1 ultra-hypermutated phenotype (e.g., tumor mutational burden > 50 mut/Mb) AND therapy will be used in combination with nivolumab (for 4 doses followed by nivolumab as a single agent).MSI-H/dMMR or POLE/POLD1 or TMB > 50 mut/Mb

6 month authorization.

Initial Approval — Mesothelioma

Authorization of 6 months may be granted for pleural or peritoneal mesothelioma when ALL of the following apply:

Mesothelioma: Used in combination with nivolumab for treatment of pleural or peritoneal mesothelioma, including pericardial mesothelioma and tunica vaginalis testis mesothelioma.

6 month authorization.

Initial Approval — Hepatocellular Carcinoma

Authorization of 6 months may be granted for hepatocellular carcinoma when ANY of the following apply:

Hepatocellular carcinoma: First-line treatment of unresectable or extrahepatic/metastatic disease in combination with nivolumab (for 4 doses followed by nivolumab as a single agent) OR used as subsequent treatment after sorafenib as described in labeling.

6 month authorization; two scenarios described (first-line and subsequent).

Pleural or Peritoneal Mesothelioma

Covered indications (examples from document) when ALL specified conditions are met:

Pleural or Peritoneal Mesothelioma: Authorization of 6 months may be granted in combination with nivolumab for treatment of pleural or peritoneal mesothelioma, including pericardial mesothelioma and tunica vaginalis testis mesothelioma.6 months

combination with nivolumab

Hepatocellular Carcinoma

Hepatocellular Carcinoma: Authorization of 6 months may be granted for first-line treatment of unresectable or extrahepatic metastatic disease in combination with nivolumab (for 4 doses followed by nivolumab as a single agent).6 months

combination then nivolumab monotherapy

MSI-H / dMMR Indications

MSI-H / dMMR tumor indications: Authorization of 6 months may be granted in combination with nivolumab for MSI-H or dMMR tumors including small bowel adenocarcinoma, ampullary adenocarcinoma, and gastric cancer.6 months

biomarker-defined approvals

TMB-H Indications

TMB-H tumor indications: Authorization of 6 months may be granted in combination with nivolumab for tumors with tumor mutation burden-high (TMB-H) including some bone and biliary tract cancers; specific TMB thresholds referenced in document (e.g., >50 mut/Mb) guide eligibility.TMB-H

some inconsistent numeric notations present

Merkel Cell Carcinoma

Merkel Cell Carcinoma: Authorization of 6 months may be granted as a single agent or in combination with nivolumab (for 4 doses followed by nivolumab as a single agent) for treatment of primary node-positive regional, unresectable, recurrent, or stage IV disease.6 months

allows single-agent or combination

Continuation/Reauthorization Criteria

Continuation of therapy — reauthorization conditions:

General continuation: Authorization of 6 months may be granted for continued treatment when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.6 months

varies by indication up to stated maximums

Adjuvant melanoma: Up to 3 years total may be authorized for adjuvant melanoma reauthorization requests when no unacceptable toxicity or progression is present.up to 3 years

applies to adjuvant melanoma

NSCLC, gastric/esophagogastric junction, pleural mesothelioma: Continuation may be authorized up to 24 months total for these indications when no unacceptable toxicity or progression is present.up to 24 months

This medical policy applies to benefits administered by Wellmark Blue Cross and Blue Shield. Benefit determinations are based on the applicable contract language in effect at the time services were rendered, and exclusions, limitations, or exceptions in the member's contract may affect coverage. This policy may not apply to the Federal Employee Program (FEP); benefits for FEP members are determined by the Federal Employee Program and may differ from the provisions described here.

Not medically necessary — Yervoy (ipilimumab) is considered not medically necessary when the member does not meet the specific clinical criteria and documentation requirements set forth in this policy. Requests that do not satisfy the stated indication-specific eligibility, required molecular testing, dosing or sequencing limits, or other policy conditions should be denied as not medically necessary.

Yervoy (ipilimumab) is considered not medically necessary for members who do not meet the criteria described in this policy. Coverage decisions require that the member meet the applicable indication-specific criteria and any required documentation; absence of those elements supports a determination of not medically necessary.

Coding

Covered HCPCS CodesHCPCSCovered

J9228

Injection, ipilimumab, 1mg

TMB — TMB-H thresholds

Documented TMB threshold (consistent)> 50 mut/Mb referenced for eligibility in ultra-hypermutated / TMB-H tumors (e.g., small bowel adenocarcinoma).

Inconsistent numeric notation in sourceOne explicit notation shows '210 mutations/megabase (mut/Mb)' which appears inconsistent with other references and is likely a typographic error.

Contextual usesTMB-H status is used to qualify tumors (bone, biliary tract, small bowel and others) for combination therapy with nivolumab per the policy.

Provider Actions & Requirements

Prior Authorization

Prior Authorization Required — 6‑Month Standard

Prior authorization is required. Initial approvals are commonly granted for 6 months when the member and treatment meet the specific clinical criteria listed in the policy. Subsequent authorizations are generally granted in 6-month increments when continued treatment meets the applicable continuation criteria and there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

Standard initial authorization duration: 6 months for indications listed in Criteria for Initial Approval.
Reauthorization: generally in 6-month increments when criteria continue to be met.
Combination inductions with nivolumab: authorization commonly covers induction (approximately 4 doses) followed by nivolumab monotherapy per the indication.

Denial Risk

Benefit / Contract Exclusions

Benefits and coverage are determined by the member's contract. Coverage may vary by plan; exclusions, limitations, or exceptions in the contract take precedence. Wellmark (Blue Cross Blue Shield - Iowa) will determine medical necessity only if the benefit exists and no contract exclusions apply. Confirm member eligibility and benefits prior to submitting a prior authorization request.

Background

Ipilimumab (Yervoy) is a recombinant human monoclonal antibody that targets cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4). By binding CTLA-4 and blocking its interaction with ligands, ipilimumab augments T‑cell activation and proliferation, producing an immune-mediated antitumor effect. The intent of this policy is to ensure appropriate patient selection and utilization of ipilimumab in accordance with FDA labeling, recognized clinical guidelines, and available evidence, by defining indication-specific criteria, required molecular testing, dosing and sequencing limits, and prior authorization requirements.

Definitions

Ipilimumab mechanism

Mechanism summaryIpilimumab (Yervoy) is a recombinant human monoclonal antibody that binds CTLA-4 and blocks its interaction with ligands (CD80/CD86), augmenting T-cell activation and proliferation.

Drug classCTLA-4 inhibitor; immune checkpoint inhibitor.

Clinical intentUsed to enhance antitumor immune response by releasing CTLA-4–mediated inhibition of T-cell activation.

Tumor mutation burden–high (TMB-H) definition and note on numeric discrepancy

Primary definition used in policyTMB-H is referenced as tumor mutation burden–high used to qualify tumors for ipilimumab plus nivolumab therapy (policy examples include eligibility when TMB > 50 mut/Mb).

Alternate numeric notation in sourceThe source contains an inconsistent explicit value shown as '210 mutations/megabase (mut/Mb)' which likely represents a typographic error and is not consistent with the '> 50 mut/Mb' threshold used elsewhere.

Initial Therapy Criteria

Initial therapy and authorization duration

Initial authorization typically granted for 6 months when the specific indication criteria and required molecular testing/documentation are met.

Initial therapy general: Initial approvals generally for 6 months per indication when criteria (as listed per indication) are satisfied and documentation provided.6 months

See individual indication nodes for specifics.

Initial therapy

Initial authorization commonly for 6 months; many indications specify combination with nivolumab and biomarker requirements.

General initial authorization: Authorization of 6 months may be granted for listed indications, frequently when used in combination with nivolumab (often for 4 doses followed by nivolumab monotherapy).6 months

Continuation / Reauthorization Criteria

Continuation therapy limits

Continuation (reauthorization) rules vary by indication and total allowed duration.

Adjuvant melanoma continuation: May be authorized up to 3 years when no unacceptable toxicity or progression on current regimen.up to 3 years

Cutaneous melanoma, RCC, colorectal, hepatocellular continuation: Authorization of 6 months may be granted (up to 4 doses maximum if member has not already received 4 doses) when no unacceptable toxicity or progression is present.up to 4 doses if not already received

specific to listed cancers

NSCLC, gastric/esophagogastric junction, pleural mesothelioma continuation: Authorization may be granted up to 24 months total when no unacceptable toxicity or progression is present.

Step Therapy & Sequencing

Requirement	Details	Coverage status
Indication context
Low-dose ipilimumab used in combination with pembrolizumab for disease progression after prior anti–PD-1 therapy (metastatic or unresectable cutaneous melanoma)
Notes on dosing and sequencing
Used at low dose in combination with pembrolizumab as subsequent therapy following anti–PD-1 therapy; preserves policy-specified low-dose combination sequencing

Requirement	Details	Coverage status
Indication context
Combination induction with nivolumab for multiple indications (e.g., cutaneous melanoma, uveal melanoma, CNS brain metastases, renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, mesothelioma, Merkel cell carcinoma)
Induction regimen
Authorization describes combination induction of approximately 4 doses of ipilimumab plus nivolumab followed by nivolumab monotherapy (policy preserves 4-dose induction then transition to single-agent nivolumab)

OpenPayer

Yervoy (ipilimumab) — Coverage Criteria

Coverage Criteria

Coding

Provider Actions & Requirements

Background

Definitions

Initial Therapy Criteria

Continuation / Reauthorization Criteria

Step Therapy & Sequencing