CurrentAnthemPolicy CC-0125

Opdivo (nivolumab)

Clinical drug policy summarizing FDA indications and NCCN compendia recommendations for nivolumab (Opdivo) across a wide range of malignancies, including single-agent and combination uses (noting Qvantig subcutaneous formulation separately). This part (1 of 3) covers numerous tumor types, recommended lines of therapy, biomarker-based indications (e.g., MSI-H/dMMR, TMB-H, PD-L1), and definitional measures.

Policy Summary

PayerAnthem

PolicyOpdivo (nivolumab)

Policy CodePolicy CC-0125

Change TypeRevised

Effective Date03/26/2026

Next Review DateN/A

Key ActionDocument MSI-H/dMMR, TMB, PD-L1 and prior therapies/line of therapy and verify tumor-specific NCCN/label criteria for prior authorization.

SourceLink

POLICY UPDATE CHANGES

Document status shown as Revised with publish date 03/26/2026 and last review date 02/20/2026.

02/20/2026 Annual Review: separated NCCN recommendation for ampullary adenocarcinoma criteria; updated bone cancer combination use with sunitinib; clarified NCCN biliary tract, cervical, colorectal, uterine neoplasm criteria; removed lymphocyte predominant Hodgkin lymphoma criteria; added multiple new NCCN recommendations and clarifications.

08/15/2025 Select Review: added TMB clarification to POLE/POLD1 mutations and updated combination use in relapsed refractory Hodgkin lymphoma; wording/formatting updates.

05/16/2025 Select Review: two new FDA indications added for colorectal cancer and first-line hepatocellular carcinoma in combination with ipilimumab; multiple NCCN criteria updates across tumor types.

02/21/2025 Annual Review: updated NCCN criteria for ampullary adenocarcinoma, biliary tract, bladder, bone, colorectal, endometrial, esophageal cancers and many others; added multiple NCCN recommendations and clarified performance status requirements for some indications.

11/15/2024 Select Review: FDA approval added for neoadjuvant use with platinum-doublet chemo and adjuvant nivolumab in resectable NSCLC (tumors ≥4 cm and/or node positive) with exclusions for EGFR/ALK.

03/11/2024 Select Review: FDA approval for first-line in unresectable/metastatic urothelial carcinoma with cisplatin and gemcitabine; other NCCN changes.

02/23/2024 Annual Review: multiple NCCN 2A additions and changes across tumor types including Anal carcinoma, biliary tract cancers, cervical cancer, gastric cancers, and Hodgkin lymphoma.

11/19/2023 Select Review: updated resected melanoma criteria per FDA adjuvant approval (stage IIB,IIC,III,IV) and removed 1-year duration requirement.

Multiple prior revisions (2020-2023) documented updates for new FDA approvals, NCCN recommendations, coding additions/removals, and indication clarifications across many tumor types.

30+Tumor types mentioned

MultipleBiomarker-driven indications

FDA & NCCNSource alignment

0-2ECOG requirement (common)

~80+ICD-10 codes referenced

Coverage Summary

Coverage stance: mixed. Coverage aligns with FDA approvals and NCCN compendia recommendations as summarized in the disease-specific criteria (see policy intro). The document describes numerous FDA‑labeled indications (e.g., CRC, NSCLC, ESCC, HCC, melanoma, RCC, urothelial carcinoma, mesothelioma, classical Hodgkin lymphoma) and extensive NCCN 1/2A/2B recommendations across many tumor types. The policy notes that the subcutaneous Opdivo Qvantig formulation may be substituted for IV nivolumab but that Opdivo Qvantig is a separate policy and is not indicated in combination with intravenous ipilimumab (Yervoy).

Initial Therapy Criteria

Continuation Therapy Criteria

Unproven Uses and Exclusions

Applicable Codes

Document identifiersmixed

CC-0125

Document # (internal policy identifier)

HCPCS / J-code for nivolumabHCPCS

J9299

Injection, nivolumab, 1 mg [Opdivo]

Relevant ICD-10 Diagnosis Codes (informational list)ICD-10

C00.0-C06.9	Malignant neoplasm of parts of lip and oral cavity
C09.0-C13.9	Malignant neoplasm of tonsil, pharynx, pyriform sinus
C14.0-C14.8	Malignant neoplasm of other and ill-defined sites in the lip, oral cavity and pharynx
C15.3-C15.9	Malignant neoplasm of esophagus
C16.0-C16.9	Malignant neoplasm of stomach
C17.0-C17.9	Malignant neoplasm of small intestine
C18.0-C18.9	Malignant neoplasm of colon
C19	Malignant neoplasm of rectosigmoid junction
C20	Malignant neoplasm of rectum
C21.0-C21.8	Malignant neoplasm of anus and anal canal

1–10 of 56

1/6

ICD-10-CM diagnosis codes mentioned/added/updated in this partICD-10Covered

C43.0-C43.9	Malignant melanoma of skin
C44.02	Squamous cell carcinoma of skin of lip
C44.121-C44.1292	Squamous cell carcinoma of skin of eyelid, including canthus
C44.221-C44.229	Squamous cell carcinoma of skin of ear and external auricular canal
C44.320-C44.329	Squamous cell carcinoma of skin of other and unspecified parts of face (includes C44.321-C44.329 referenced in coding updates)
C44.321-C44.329	Squamous cell carcinoma of skin of other and unspecified parts of face (explicitly added in coding reviewed)
C44.42	Squamous cell carcinoma of skin of scalp and neck
C44.520-C44.529	Squamous cell carcinoma of skin of trunk
C44.621-C44.629	Squamous cell carcinoma of skin of upper limb, including shoulder
C44.721-C44.729	Squamous cell carcinoma of skin of lower limb, including hip

1–10 of 78

1/8

Provider Actions & Prior Authorization

Prior Authorization

Clinical criteria required for prior authorization

Prior authorization is required for most uses of Opdivo (nivolumab). Submit clinical documentation that demonstrates the requested use meets plan coverage criteria and any step-therapy or utilization management requirements. Include the applicable HCPCS/J-code on the request to facilitate review.

Affected code: J9299

Documentation Required

Biomarker documentation required

Documentation of tumor biomarkers and prior therapies is required when relevant to the indication requested. Provide pathology and molecular testing results and treatment history to support that the member meets FDA or NCCN-recommended biomarker-directed indications.

MSI-H / dMMR status (eg, PCR, IHC, or NGS report)

Clinical Evidence & References

40+Tumor-specific indications listed (approx.)

30+Tumor types mentioned

~80+ICD-10 ranges/codes referenced or added in this part

2026-02-20Most recent history entry date

Evidence summary: NCCN guidelines (multiple disease‑specific versions 2024–2026) are cited throughout the policy as the primary compendia support. Key clinical trials and publications referenced include multiple CheckMate studies (eg, CheckMate 649 for gastric/GEJ/esophageal adenocarcinoma, CheckMate 204 and CheckMate 142) and pivotal trials of nivolumab and nivolumab + ipilimumab across tumor types (references list includes studies and abstracts supporting NSCLC, melanoma brain metastases, CRC MSI‑H/dMMR, anal cancer, and others). See the references section for the full list (references numbered 1–21+).

Background & Definitions

Background: Opdivo (nivolumab) is a monoclonal antibody that blocks the programmed death receptor‑1 (PD‑1) pathway, releasing inhibitory checkpoints on T cells to enhance anti‑tumor immunity. The policy documents multiple FDA approvals and extensive NCCN compendia recommendations across tumor types. Note that the subcutaneous Opdivo Qvantig formulation may be substituted for IV nivolumab but Qvantig is addressed under a separate policy and is not indicated for combination use with intravenous ipilimumab.

Term	Definition
Adjuvant therapy
Treatment given after the primary treatment to increase the chances of a cure; may include chemotherapy, radiation, hormone or biological therapy.
MSI-H/dMMR
Microsatellite instability-high or mismatch repair deficient tumors; used as biomarker to guide immunotherapy use.
TMB-H
Tumor mutational burden-high; thresholds and context specified in disease sections (eg, >50 mut/Mb for ultra-hypermutated POLE/POLD1).
ECOG
Eastern Cooperative Oncology Group Performance Status; scale 0-5 describing functional status.
Karnofsky Performance Status
Scale 0-100 measuring functional status and ability to tolerate therapies.
PD-1
Programmed death (PD)-1 proteins found on T-cells that attach to PD ligands (PD-L1) on cells and can prevent T-cells from attacking cancer cells.
PD-L1
Programmed death ligand found on cells to which PD-1 attaches; high PD-L1 can help cancer cells avoid immune attacks.
PFS
Progression free survival - time during and after treatment that an individual lives without disease worsening.
dMMR / MSI-H
Deficient mismatch repair / microsatellite instability-high tumor phenotype associated with response to checkpoint inhibitors.

Revision History

03/26/2026revisedLatest

Document status updated to Revised with publish date 03/26/2026 and last review date 02/20/2026.

02/20/2026revisedLatest

Annual Review: separated NCCN recommendation for ampullary adenocarcinoma criteria; updated bone cancer combination use with sunitinib; clarified NCCN biliary tract, cervical, colorectal, and uterine neoplasm criteria; removed lymphocyte predominant Hodgkin lymphoma criteria; added NCCN recommendations and clarifications. (Marked material change)

08/15/2025

Policy Summary

PayerAnthem

PolicyOpdivo (nivolumab)

Policy CodePolicy CC-0125

Change TypeRevised

Effective Date03/26/2026

Next Review DateN/A

Key ActionDocument MSI-H/dMMR, TMB, PD-L1 and prior therapies/line of therapy and verify tumor-specific NCCN/label criteria for prior authorization.

SourceLink

On This Page

Tumor mutational burden (TMB) result when used to justify TMB-H indications

PD-L1 testing and Tumor Proportion Score (TPS) or Combined Positive Score (CPS), if relevant to the indication

EGFR, ALK, ROS1, BRAF, HER2 and other relevant genomic alterations when required to determine targeted-therapy eligibility or exclude other options

Prior systemic therapies (agents, dates, best response) including prior checkpoint inhibitor exposure

Performance status (ECOG or Karnofsky) and brief clinical summary

Documentation Required

Biomarker and prior therapy documentation

When an indication requires both biomarker evidence and prior therapy history (for example, MSI-H/dMMR colorectal cancer after progression on fluoropyrimidine/oxaliplatin/irinotecan), include both molecular testing reports and a complete prior-therapy timeline. Lack of required biomarker or prior therapy documentation may result in denial.

Provide both molecular pathology (MSI-H/dMMR, TMB, PD-L1, or other specified tests) and detailed prior therapy records when the indication specifies previous treatment requirements
Document dates and agents for fluoropyrimidine, oxaliplatin, and irinotecan when requesting Opdivo for post‑chemotherapy metastatic MSI-H/dMMR colorectal cancer
If combination therapy with ipilimumab is requested, document absence of prior checkpoint inhibitor exposure when the regimen is contingent on no prior immunotherapy

Documentation Required

Align coverage with NCCN and FDA indications

Coverage for Opdivo is aligned with FDA approvals and NCCN recommendations. Requests that fall outside FDA indications or NCCN-supported compendia uses, or lack the required biomarker/clinical evidence per those sources, may be considered investigational or not medically necessary and denied.

Coverage decisions will follow FDA-labeled indications and NCCN compendia guidance (including required biomarker thresholds such as MSI-H, dMMR, TMB-H, or PD-L1 where specified)
Uses not supported by NCCN or the FDA, or requests without required biomarker or prior therapy documentation, are at risk for denial

Denial Risk

Denial risk for unsupported or undocumented uses

Contraindicated or unsupported uses and requests that do not meet the plan's documented clinical criteria may be denied. Denials commonly occur when required biomarker evidence, prior therapy history, or performance status criteria are missing or do not meet specified thresholds.

Denial risk for uses without supporting FDA/NCCN evidence or missing required documentation
Denial if criteria (biomarkers, prior therapies, performance status) are not met

Prior Authorization

Prior authorization required per plan UM

Use of Opdivo is subject to the plan's utilization management and prior authorization policies as allowed by law. Verify member benefits and submit PA requests per the payer's process prior to initiating therapy.

Requests must follow the plan's UM/PA procedures and include supporting clinical documentation
Prior authorization is required per the member's plan

Select Review: added TMB clarification to POLE/POLD1 mutations and updated combination use in relapsed refractory Hodgkin lymphoma; wording and formatting updates.

05/16/2025added

Select Review: two new FDA indications added for colorectal cancer and first-line hepatocellular carcinoma in combination with ipilimumab; multiple NCCN criteria updates across tumor types. (Coding additions noted)

02/21/2025revised

Annual Review: updated numerous NCCN criteria across ampullary adenocarcinoma, biliary tract, bladder, bone, colorectal, endometrial, esophageal cancers and others; clarified performance status requirements and added multiple NCCN recommendations.

11/15/2024added

Select Review: FDA approval added for neoadjuvant platinum-doublet chemotherapy and adjuvant nivolumab in resectable NSCLC (tumors ≥4 cm and/or node positive) with exclusions for EGFR/ALK.

03/11/2024added

Select Review: FDA approval for first-line use in unresectable/metastatic urothelial carcinoma with cisplatin and gemcitabine; additional NCCN changes.

02/23/2024revised

Annual Review: multiple NCCN 2A additions and changes across tumor types including Anal carcinoma, biliary tract cancers, cervical cancer, gastric cancers, and Hodgkin lymphoma.

11/19/2023added

Select Review: updated resected melanoma criteria per FDA adjuvant approval (stage IIB, IIC, III, IV) and removed 1-year duration requirement.

2020-2023revised

Multiple prior revisions documented updates for new FDA approvals, NCCN recommendations, coding additions/removals, and indication clarifications across many tumor types.