Anthem Opdivo Qvantig Coverage Update

Coverage and Medical Necessity Criteria

Covered Indications / Medical Necessity Criteria

Covered when the specific tumor-type criteria below are met (each roman numeral indicates a distinct covered indication with its own AND/OR requirements).

I. Anal carcinoma: Individual has a diagnosis of Anal carcinoma (NCCN 2A); AND is using as second-line and subsequent therapy; AND is using in metastatic disease; AND is using as a single agent; AND has not received another anti-PD-1 or anti-PDL1 agent; AND is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant.

II. Cervical cancer: Individual has a diagnosis of Cervical Cancer (NCCN 2A); AND is using as a single agent; AND is using for second-line or subsequent therapy; AND has CPS ≥ 1 for local/regional recurrence or stage IVB or recurrence with distant metastases; AND has not received another anti-PD-1 or anti-PDL1 agent; AND is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant.

III. CLL/SLL with Richter transformation: Individual has a diagnosis of Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia (CLL/SLL) (NCCN 2A); AND is using as a single agent or in combination with ibrutinib; AND is using for histologic (Richter) transformation to diffuse large B-cell lymphoma; AND meets one of the following: has del(17p)/TP53 mutation OR is chemotherapy refractory or unable to receive chemoimmunotherapy; AND has not received another anti-PD-1 or anti-PDL1 agent; AND is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant.

VI/VII. Colorectal cancer: Individual has a diagnosis of Colorectal Cancer, including advanced Appendiceal Adenocarcinoma (NCCN 2A); AND is using as monotherapy; AND meets one of the following: resectable disease for neoadjuvant or initial treatment with dMMR/MSI-H or POLE/POLD1 mutation with ultra-hypermutated phenotype (e.g., TMB > 50 mut/Mb) OR using as neoadjuvant therapy in clinical T4b disease with dMMR/MSI-H; OR is using as monotherapy in metastatic disease with dMMR or MSI-H that has progressed following fluoropyrimidine, oxaliplatin, and irinotecan; AND is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant; AND has not received another anti-PD-1 or anti-PDL1 agent.

VIII. Endometrial carcinoma: Individual has a diagnosis of recurrent MSI-H or dMMR endometrial carcinoma (NCCN 2A); AND is using as a single agent; AND is using as second-line or subsequent therapy; AND has not received treatment with another anti-PD-1 or anti-PDL1 agent; AND is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant.

IX–XVI. Esophageal and gastric cancers group: Multiple covered scenarios including: induction systemic therapy to relieve dysphagia in medically fit pre-esophagectomy patients (in combination with platinum-containing chemotherapy and capecitabine or fluorouracil or as monotherapy following prior IV nivolumab combinations); unresectable locally advanced/recurrent/metastatic ESCC in combination with fluoropyrimidine- and platinum-containing chemotherapy as first-line with ECOG 0-2 and no prior checkpoint inhibitor; single-agent second-line ESCC after progression/intolerance to fluoropyrimidine- and platinum-based chemotherapy with ECOG 0-2 or KPS 60-100; completely resected disease as single agent for residual pathologic disease post-neoadjuvant CRT with ECOG 0-2 and no prior checkpoint inhibitor; MSI-H/dMMR tumors in postoperative management after preop nivolumab+ipilimumab; advanced/metastatic gastric/EGJ in combination with fluoropyrimidine+platinum for HER2-negative disease with ECOG 0-2 and no prior checkpoint inhibitor; palliative care scenarios including MSI-H/dMMR or first-line combos or second-line single-agent use as specified.

XVII. Gestational trophoblastic neoplasia: Individual has multi-agent chemotherapy-resistant gestational trophoblastic neoplasia (NCCN 2A) with recurrent or progressive intermediate trophoblastic tumor or high-risk disease; AND is using as single-agent therapy; AND has not received another anti-PD-1 or anti-PDL1 agent; AND is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant.

XVIII. Advanced hepatocellular carcinoma: Individual has advanced hepatocellular carcinoma (Label, NCCN 2A); AND is using as a single agent in those classified as Child-Pugh Class B; AND has a current ECOG performance status of 0-2; AND has not received treatment with another anti-PD-1 or anti-PDL1 agent; AND is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant.

XIX–XXVII. Hematologic and other solid tumor indications: Multiple indications including Hodgkin lymphoma (relapsed/refractory adult and pediatric) as single agent or with brentuximab vedotin or ICE; relapsed/refractory Kaposi sarcoma as subsequent single-agent therapy excluding MCD/KICS; malignant pleural/peritoneal mesothelioma subsequent single-agent therapy with ECOG 0-2; unresectable/metastatic melanoma single agent with ECOG 0-2 and no prior anti-PD-1/PD-L1; metastatic melanoma with asymptomatic brain metastases as monotherapy; Merkel cell carcinoma single agent for metastatic/recurrent locoregional disease not amenable to definitive surgery/radiation with ECOG 0-2; NSCLC recurrent/advanced/metastatic single agent after progression on platinum chemotherapy; resected melanoma adjuvant for stages IIB-IV as single agent; metastatic NSCLC with brain metastases single agent for PD-L1 ≥1% tumors; primary mediastinal large B-cell lymphoma relapsed/refractory pediatric aggressive B-cell lymphoma as single agent or consolidation with brentuximab vedotin; renal cell carcinoma advanced/metastatic monotherapy with clear-cell component after 1-2 prior anti-angiogenic regimens with ECOG 0-2; and other listed settings — most require no prior anti-PD-1/PD-L1 and no systemic immunosuppressant therapy.

XXVIII. Neoadjuvant/resectable NSCLC: Individual has resectable NSCLC and is using nivolumab as neoadjuvant therapy (Label, NCCN 2A) in combination with platinum-doublet chemotherapy (e.g., paclitaxel and carboplatin); resectable defined as tumors ≥4 cm or node positive; AND has no known EGFR mutations or ALK rearrangements; AND continues nivolumab as a single agent for adjuvant treatment after surgery; AND has current ECOG 0-2; AND has not received treatment with another anti-PD-1 or anti-PDL1 agent; AND is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant.

RCC combination with cabozantinib: Individual has relapsed, recurrent, or advanced RCC using nivolumab in combination with cabozantinib as first-line or subsequent therapy with current ECOG performance status 0-2; AND has not received treatment with another anti-PD-1 or anti-PDL1 agent; AND is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant.

XXX. Small bowel adenocarcinoma: Individual has advanced or metastatic small bowel adenocarcinoma (NCCN 2A) with dMMR/MSI-H or POLE/POLD1 ultra-hypermutated phenotype (e.g., TMB > 50 mut/Mb); AND is using as monotherapy; AND has current ECOG performance status of 0-2; AND has not received treatment with another anti-PD-1 or anti-PDL1 agent; AND is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant.

XXXI. Extranodal NK/T-cell lymphoma: Individual has relapsed/refractory extranodal NK/T-cell lymphoma (NCCN 2A); AND is using nivolumab as monotherapy following alternate combination chemotherapy not previously used (e.g., asparaginase-based regimen); AND has not received treatment with another anti-PD-1 or anti-PDL1 agent; AND has current ECOG performance status of 0-2; AND is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant.

XXXII. SCCHN and head & neck cancers: Individual has recurrent, unresectable, or metastatic squamous cell carcinoma of the head and neck (SCCHN) (Label, NCCN 1); AND is using as monotherapy with confirmation of disease progression on or after platinum-containing chemotherapy OR is using in combination with cetuximab (NCCN 2A); AND may be used for first- and subsequent-line therapy; AND has current ECOG performance status of 0-2; AND has not received another anti-PD-1 or anti-PDL1 agent; AND is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant.

Anaplastic thyroid carcinoma (metastatic): Individual has metastatic anaplastic thyroid carcinoma (NCCN 2A); AND is using as a single agent; AND has current ECOG performance status of 0-2; AND has not received another anti-PD-1 or anti-PDL1 agent; AND is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant.

Indication-specific medical necessity criteria (selected examples from document)

Covered when ALL of the following are met for a given tumor-specific indication as outlined below

dMMR/MSI-H or POLE/POLD1 ultra-hypermutated colorectal or small bowel adenocarcinoma: Individual has advanced or metastatic disease with dMMR/MSI-H or POLE/POLD1 mutation with ultra-hypermutated phenotype (e.g., TMB > 50 mut/Mb); AND is using as monotherapy; AND has current ECOG performance status of 0-2; AND has not received treatment with another anti-PD-1 or anti-PDL1 agent; AND is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant.

Extranodal NK/T-cell lymphoma: Relapsed/refractory disease; AND is using nivolumab as monotherapy following alternate combination chemotherapy not previously used (e.g., asparaginase-based regimen); AND has not received treatment with another anti-PD-1 or anti-PDL1 agent; AND has current ECOG performance status of 0-2; AND is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant.

Squamous cell carcinoma of the head and neck (SCCHN): Recurrent, unresectable, or metastatic SCCHN; AND is using monotherapy with confirmation of progression on or after platinum-containing chemotherapy OR is using in combination with cetuximab (NCCN 2A); AND may be used first- or subsequent-line; AND has current ECOG performance status of 0-2; AND has not received another anti-PD-1 or anti-PDL1 agent; AND is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant.

Opdivo (nivolumab) is not covered for members who are actively receiving therapy for an autoimmune disease or other chronic condition that requires treatment with a systemic immunosuppressant. Multiple indication-specific criteria in this policy explicitly require that the individual is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant as a condition of approval, and absence of such therapy must be documented during prior authorization review.

Opdivo Qvantig (nivolumab with hyaluronidase) may not be approved when used in combination with intravenous ipilimumab (Yervoy). The policy explicitly lists combination use with IV ipilimumab as a non‑approved regimen and requires single‑agent or other specified, documented combinations consistent with the tumor‑specific criteria for coverage.

For most covered indications in this policy, prior receipt of another anti‑PD‑1 or anti‑PD‑L1 agent disqualifies the request. The criteria repeatedly state that the individual has not received another anti‑PD‑1 or anti‑PD‑L1 agent as a requirement for approval and documentation of prior checkpoint inhibitor exposure must be provided for authorization decisions.

Any use of Opdivo Qvantig that does not meet the listed, tumor‑specific criteria — including required biomarker status, line/sequence of therapy, ECOG performance status, or documented absence of prior anti‑PD‑1/PD‑L1 exposure — may be denied as not medically necessary. In addition, non‑approved combinations (for example, Opdivo Qvantig with intravenous ipilimumab) are specifically noted as situations in which the product may not be approved.

Billing and Diagnosis Codes

No specific CPT/HCPCS/ICD-10 codes listed in this excerptmixed

No codes listed

HCPCS for productHCPCS

J9289

Injection, nivolumab, 2 mg and hyaluronidase-nvhy [Opdivo Qvantig]

Applicable ICD-10-CM diagnosis code rangesICD-10

C00.0-C06.9	Malignant neoplasm of lip, tongue, oral cavity
C09.0-C13.9	Malignant neoplasm of tonsil, oropharynx, nasopharynx, pyriform sinus, hypopharynx
C14.0-C14.9	Malignant neoplasm of other and ill-defined sites in the lip, oral cavity and pharynx
C15.3-C16.9	Malignant neoplasm of esophagus, stomach
C17.0-C20	Malignant neoplasm of small intestine, colon, rectosigmoid junction, rectum
C21.0-C21.8	Malignant neoplasm of anus and anal canal
C22.0	Liver cell carcinoma
C22.8	Malignant neoplasm of liver, primary, unspecified as to type
C22.9	Malignant neoplasm of liver, not specified as primary or secondary
C30.0	Malignant neoplasm of nasal cavity

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Tumor mutational burden (TMB) — > 50 mut/Mb (example for ultra-hypermutated phenotype)

Threshold> 50 mut/Mb

ContextExample threshold for ultra-hypermutated phenotype associated with POLE/POLD1 mutations

Applicable tumor typesColorectal cancer and small bowel adenocarcinoma referenced for POLE/POLD1 ultra-hypermutated phenotype

PD-L1 Combined Positive Score (CPS) — >= 1%

Threshold>= 1% (PD-L1 Combined Positive Score [CPS])

Applicable indicationsVaginal cancer (recurrent/metastatic) and other indications where CPS is specified

Prior Authorization, Documentation, and Provider Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Coverage is limited to the tumor-specific indications and clinical criteria listed in this policy. Opdivo Qvantig (nivolumab and hyaluronidase‑nvhy) will not be approved when used outside the listed indications or when required criteria are not met.

Prior authorization required for Opdivo Qvantig (HCPCS J9289) — approval contingent on meeting indication-specific clinical criteria (diagnosis, line/sequence of therapy, ECOG 0-2, prior therapy history, biomarker status where required).
Coverage limited to the listed tumor-specific criteria (e.g., required biomarkers such as dMMR/MSI-H, POLE/POLD1 mutations or defined TMB thresholds; required prior lines of therapy or confirmation of progression on platinum-containing chemotherapy where specified).
Non-approved combinations/indications: Opdivo Qvantig is not approved in combination with intravenous ipilimumab (Yervoy). Use will also be denied when the policy's criteria are not met or for any indications not listed in the policy.
Required clinical documentation to support medical necessity: documentation of diagnosis, disease stage (metastatic/recurrent as applicable), ECOG performance status (0–2) or Karnofsky 60–100, prior therapies and dates (including confirmation of progression where line/sequence criteria apply), prior exposure to other anti‑PD‑1/PD‑L1 agents, and biomarker results when required (e.g., dMMR/MSI‑H, POLE/POLD1 mutation status, PD‑L1 CPS, TMB).
Additional documentation: evidence that the patient is not receiving therapy for an autoimmune disease or other condition requiring systemic immunosuppression, and any other indication‑specific prerequisites (e.g., Child‑Pugh class for hepatocellular carcinoma, confirmation of resectability status for neoadjuvant use).

Background and Scope

Nivolumab is an anti‑PD‑1 immune checkpoint inhibitor covered for multiple malignancies when the indication‑specific medical necessity criteria are met. Coverage requires adherence to tumor‑type criteria that frequently include: documentation of appropriate biomarkers (e.g., dMMR/MSI‑H, POLE/POLD1 mutation with ultra‑hypermutated phenotype) where specified, confirmation of required line/sequence of therapy, and acceptable performance status (commonly ECOG 0–2). Requests are subject to prior authorization and must include clinical documentation supporting diagnosis, prior therapies, biomarker results, and ECOG as applicable.

Clinical Definitions and Thresholds

dMMR/MSI-H — Deficient mismatch repair / microsatellite instability-high tumor status required for several tumor-specific indications.

DefinitionDeficient mismatch repair / microsatellite instability-high (dMMR/MSI-H)

Required forSeveral tumor-specific indications including colorectal, endometrial, gastric/EGJ postoperative management, and small bowel adenocarcinoma

DocumentationClinical documentation of dMMR/MSI-H required when specified for indication approval

ECOG performance status 0-2 — A performance status threshold commonly required to qualify for therapy as specified in multiple indications.

Threshold/scoreECOG performance status 0-2

Usage

Line and Sequence Requirements

first-line | second-line | salvage

First-line/combo therapy: Some indications specify first-line use in combination with fluoropyrimidine- and platinum-containing chemotherapy (e.g., unresectable ESCC, gastric/EGJ, select palliative gastric scenarios); or first-line use in combination with cabozantinib for RCC per specified criteria.

Second-line or subsequent therapy: Multiple tumor indications specify use as second-line or subsequent therapy (examples include anal carcinoma, cervical cancer, endometrial carcinoma, vaginal cancer, Merkel cell carcinoma, and single-agent second-line ESCC); approval requires meeting the indication-specific criteria (e.g., biomarker status, prior therapies, ECOG 0-2) and absence of prior anti-PD-1/PD-L1 therapy.

mixed

first- or subsequent-line as specified: Some indications allow first- or subsequent-line use (for example, SCCHN may be used first- or subsequent-line; certain gastric/EGJ and urothelial scenarios include first-line combination regimens). Approval requires the specific line(s) of therapy stated in the indication to be met and documentation of prior treatments where indicated.

Biomarker and Molecular Testing Requirements

dMMR/MSI-H

DefinitionDeficient mismatch repair / microsatellite instability-high (dMMR/MSI-H)

Required forColorectal, endometrial, small bowel adenocarcinoma and other tumor-specific indications where specified

DocumentationBiomarker results must be provided when required for prior authorization

POLE/POLD1 mutation or ultra-hypermutated phenotype — > 50 mut/Mb (example cited)

MarkerPOLE/POLD1 mutation or ultra-hypermutated phenotype

Threshold example> 50 mut/Mb (ultra-hypermutated phenotype cited)

Permitted Regimens and Combinations by Tumor Type

Indication	Covered Regimen	Coverage Status
Esophageal and esophagogastric junction cancers (induction/preoperative)	Induction systemic therapy to relieve dysphagia in medically fit patients planned for esophagectomy: nivolumab in combination with platinum-containing chemotherapy and capecitabine or fluorouracil; or nivolumab monotherapy following prior IV nivolumab in combination with ipilimumab or platinum-containing chemotherapy.	Covered
Unresectable locally advanced, recurrent, or metastatic ESCC (first-line)	Nivolumab in combination with fluoropyrimidine- and platinum-containing chemotherapy as first-line treatment (ECOG 0-2; no prior checkpoint inhibitor therapy).	Covered
Unresectable locally advanced, recurrent, or metastatic ESCC (second-line)	Nivolumab as single-agent second-line or subsequent therapy after progression on or intolerance to fluoropyrimidine- and platinum-based chemotherapy (ECOG 0-2 or KPS 60–100).	Covered
Completely resected Esophageal/EGJ cancers (postoperative/residual disease)	Nivolumab as single agent for residual pathologic disease after neoadjuvant chemoradiotherapy (CRT); ECOG 0-2; no prior anti-PD-1/PD-L1.	Covered
Advanced/metastatic Gastric or Esophagogastric Junction cancers (HER2-negative)	Nivolumab in combination with fluoropyrimidine- and platinum-containing chemotherapy for advanced/metastatic disease (HER2 negative; ECOG 0-2; no prior checkpoint inhibitor therapy).	Covered

Indication	Covered Regimen	Coverage Status
Renal cell carcinoma (advanced/metastatic) — monotherapy setting	Nivolumab monotherapy for advanced or metastatic RCC with histologic confirmation of a clear‑cell component after disease progression following one or two prior anti‑angiogenic regimens (e.g., axitinib, bevacizumab, pazopanib, sorafenib, sunitinib); ECOG 0‑2; no prior anti‑PD‑1/PD‑L1.	Covered
Renal cell carcinoma (relapsed/recurrent/advanced) — combination with cabozantinib	Nivolumab in combination with cabozantinib as first‑line or subsequent therapy for relapsed, recurrent, or advanced RCC (ECOG 0‑2; no prior anti‑PD‑1/PD‑L1; applicable even after prior immune‑oncology therapy in specified subsequent‑line combinations).	Covered

Indication	Covered Regimen	Coverage Status
Nasopharyngeal carcinoma (recurrent/unresectable/oligometastatic/metastatic)	Nivolumab in combination with cisplatin and gemcitabine for patients with no surgery or radiotherapy options; no prior anti‑PD‑1/PD‑L1 therapy required.	Covered

Indication	Covered Regimen	Coverage Status
Squamous cell carcinoma of the head and neck (SCCHN) — post‑platinum progression	Nivolumab as single‑agent therapy for recurrent, unresectable, or metastatic SCCHN after progression on or after platinum‑containing chemotherapy (ECOG 0‑2; no prior anti‑PD‑1/PD‑L1).	Covered
SCCHN — combination option	Nivolumab in combination with cetuximab (NCCN 2A) as an alternative first‑ or subsequent‑line regimen for recurrent, unresectable, or metastatic disease (ECOG 0‑2; no prior anti‑PD‑1/PD‑L1).	Covered

Indication	Covered Regimen	Coverage Status
Non‑clear cell renal cell carcinoma (nccRCC), including HLRCC	Nivolumab as single‑agent systemic therapy or in combination with cabozantinib for relapsed or metastatic nccRCC; no prior anti‑PD‑1/PD‑L1; not receiving systemic immunosuppressant therapy.	Covered

OpenPayer

Opdivo Qvantig (nivolumab hyaluronidase-nvhy) — Medical Necessity and Coverage Criteria