CurrentPremera BluecrossPolicy 5.01.591

MEDICAL POLICY 5.01.591 Immune Checkpoint Inhibitors

Defines medical necessity and site-of-service review criteria for multiple immune checkpoint inhibitor drugs (IV and SC) including indications, age limits, required diagnostic testing (e.g., PD-L1, dMMR, TMB-H), and medically necessary vs not medically necessary sites for administration. Applies to medical-benefit reviews and specifies exceptions for Alaska fully-insured members for site-of-service criteria.

Policy Summary

PayerPremera Bluecross

PolicyMEDICAL POLICY 5.01.591 Immune Checkpoint Inhibitors

Policy CodePolicy 5.01.591

Change TypeIndication additions, removals, SOS criteria, coding updates

Effective DateOct 3, 2025

Next Review DateN/A

Key ActionObtain required site-of-service and medical-necessity reviews and submit medical records documenting diagnosis, history, exam and medication history when requesting coverage.

POLICY UPDATE CHANGES

2019 Update: Added Keytruda indication for esophageal cancer; Bavencio moved into this policy and new indication for renal cell carcinoma added.

2020 Update: Added Tecentriq indication for BRAF V600 mutation-positive unresectable or metastatic melanoma in combination with cobimetinib and vemurafenib.

2021 Update: Multiple additions and removals including Keytruda esophageal/GEJ indication addition, removal of Keytruda small cell cancer coverage, additions to Libtayo and Opdivo, and removals from Imfinzi and Tecentriq for certain indications.

2022 Update: Removed Keytruda as 3rd line monotherapy for PD-L1 positive gastric/GEJ cancer; added site of service review for Keytruda and Opdivo.

2023 Update: Updated coverage criteria to include Tecentriq for ASPS (ages >=2), Keytruda adjuvant NSCLC indication, Keytruda combination with enfortumab vedotin for urothelial carcinoma, and added coverage criteria for Zynyz.

Multiple new FDA indications added for agents including Opdivo, Keytruda, Tecentriq Hybreza, Tevimbra, Imfinzi, Yervoy, Unloxcyt and others across 2022-2025.

Coverage removed when FDA indications withdrawn for multiple agents (e.g., Imfinzi for urothelial carcinoma; Tecentriq for several withdrawn indications; Keytruda 3rd-line gastric/GEJ).

Site-of-service medical necessity criteria added or expanded to include several additional agents and clarified applicability to injection drugs; Alaska exception added.

Multiple HCPCS/J-code additions and removals reflecting coding updates through 07/2025.

>20Checkpoint inhibitor products referenced

2019-2025Indication years documented in history

13+Age threshold for SOS review

PD-L1/dMMR/TMB-HBiomarker requirements present

MultipleAgents covered (listed in this part)

Coverage Summary

Policy subject: Immune checkpoint inhibitors (PD‑1, PD‑L1, CTLA‑4, LAG‑3 inhibitors) administered IV or subcutaneously; defines drug‑specific medical necessity and site‑of‑service (SOS) review rules. Status: CURRENT. Effective date: 2025-10-03; Last review: 2025-07-08.

Scope summary: Defines medical necessity and site‑of‑service review criteria for multiple immune checkpoint inhibitor products, including indications, age limits, required biomarker testing (e.g., PD‑L1, dMMR, TMB‑H), and medically necessary versus not‑medically‑necessary sites for administration. Applies to the medical benefit (drugs managed through the medical benefit).

Site‑of‑service applicability: SOS criteria applies only to medical benefit reviews and is applied for IV and injectable checkpoint inhibitors (including specified IV and SC products); SOS review of site of service is performed for individuals aged 13 years and older per the policy. The policy lists preferred medically necessary sites (physician's office, infusion center, home infusion) and circumstances when a hospital‑based outpatient setting is medically necessary.

Alaska exception: The Site‑of‑Service Medical Necessity criteria does NOT apply to Alaska fully‑insured members; those members should refer to the infusion and injection drug medical necessity criteria (Alaska HB 226 exception).

Key thresholds and approval facts

Age threshold for SOS review13 years and older

Common drug age requirementMany indications require age ≥18 years; some drug-specific indications available for ≥12 years (e.g., melanoma, MCC, other pediatric allowances)

PD-L1 / biomarker thresholds examplesPD-L1 TPS ≥50% for some NSCLC indications; PD-L1 ≥1% or ≥10% for other indications as specified; FDA-approved testing required for certain indications

dMMR requirementMismatch repair deficient (dMMR) required for some agent indications and FDA-approved testing required for coverage determination

TMB-H definitionTMB-H defined as ≥10 mutations/megabase (mut/Mb) per Keytruda indication

Unloxcyt dosing limitDose limited to 1,200 mg administered every 3 weeks

Approval duration rulesNon-formulary exception reviews may be approved up to 12 months; reauthorization (non-formulary and other reviews) may be approved up to 12 months if criteria met and chart notes show continued positive clinical response

Site-of-Service and Drug-specific Medical Necessity

Site of Service (SOS) medical necessity for infusion/injection

Site of service is medically necessary when ALL of the following are met or when listed specific clinical circumstances exist:

ALL of the following

Applies only to medical benefit reviews (SOS criteria does NOT apply to Alaska fully-insured members)
Review of site of service for individuals aged 13 years and older

Medically necessary sites of service

Physician's office
preferred medically necessary site for specified drugs

Provider Actions and Authorization Requirements

Prior Authorization

Site-of-service review and medical necessity review required

IV and other injectable immune checkpoint inhibitors are subject to site-of-service (SOS) medical necessity review for all members except Alaska fully-insured members. SOS review evaluates whether the location of drug administration (hospital outpatient department, infusion center, physician office, or home infusion) is medically necessary and appropriate. Keytruda (pembrolizumab), Opdivo (nivolumab), Imfinzi (durvalumab), Jemperli (dostarlimab-gxly), Tecentriq (atezolizumab) and formulations noted in this policy are SOS-reviewed unless administered concurrently with other IV or injectable cancer medications.

SOS review applies to members aged ≥13 for site-of-service determination.
Hospital-based outpatient setting is medically necessary for initial course or re-initiation after ≥6 months, when no outpatient infusion center is within 50 miles and no contracted home infusion agency will travel, or when clinical risk factors exist (see CRS and high-risk conditions).
When SOS criteria are not met, outpatient infusion center, physician office, or home infusion are preferred sites per policy.

Coding (HCPCS / J-codes)

HCPCS / J-codes listed for policy drugsHCPCS

C9399	Unclassified drugs or biologicals (use to report: Tecentriq Hybreza and penpulimab-kcqx)
J3263	Injection, toripalimab-tpzi (Loqtorzi), mg
J9022	Injection, atezolizumab (Tecentriq), 10 mg
J9023	Injection, avelumab (Bavencio), 10 mg
J9024	Injection, atezolizumab, 5 mg and hyaluronidase-tqjs (Tecentriq Hybreza) (new code effective 04/01/25)
J9119	Injection, cemiplimab-rwlc (Libtayo), mg
J9173	Injection, durvalumab (Imfinzi), 10 mg
J9228	Injection, ipilimumab (Yervoy), 1 mg
J9271	Injection, pembrolizumab (Keytruda), mg
J9272	Injection, dostarlimab-gxly (Jemperli), 10 mg

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Background and Clinical Evidence

Background: The policy covers immune checkpoint inhibitors and provides medical necessity criteria and site‑of‑service review rules for their administration. The Introduction includes non‑policy educational material explaining chemotherapy and immunotherapy (immune checkpoint inhibitors) for general knowledge but states that the Introduction is not coverage criteria.

The policy’s purpose: To establish agent‑specific coverage criteria (indications, age limits, biomarker/testing requirements, dosing/administration adherence to FDA labeling) and to implement a site‑of‑service program that directs preferred sites (physician office, infusion center, home infusion) and specifies when hospital‑based outpatient infusion is medically necessary or when SOS review is required.

Operational note: The drugs in this policy are managed under the medical benefit, and the policy lists specific products subject to SOS review (examples include Keytruda, Opdivo, Imfinzi, Tecentriq and their SC formulations). The SOS program clarifies exceptions (e.g., when used concurrently with other IV cancer medications) and documents Alaska fully‑insured member exemption.

Study / Evidence	Key Findings
Unloxcyt CK-301-101 ORR	mCSCC ORR 47% (95% CI: 36,59); laCSCC ORR 48% (95% CI: 30,67); median DOR not reached for mCSCC; median DOR 17.7 months for laCSCC
Zynyz PODIUM-201 ORR	Objective response rate 52% (18% CR, 34% PR); 76% of responders had duration of response ≥6 months; 62% had duration of response ≥12 months
Loqtorzi JUPITER-02 outcomes	Combination with chemotherapy reduced risk of progression or death by 48% vs chemotherapy; 37% reduction in risk of death versus chemotherapy
Penpulimab NPC PFS	Median progression-free survival 9.6 months for penpulimab arm versus 7.0 months for placebo; 12-month PFS rate 31% vs 11%
NEJM 2024	Published evidence for nivolumab plus ipilimumab in MSI-H metastatic colorectal cancer supporting coverage addition of the combination for first-line MSI-H/dMMR metastatic CRC
NCCN	Referenced NCCN Drugs & Biologics Compendium and Colon Cancer v5.2024 as guideline support for checkpoint inhibitor use (e.g., nivolumab+ipilimumab in MSI-H CRC)

Policy definitions

Site of Service (SOS)Location where the drug is administered (hospital-based outpatient setting, infusion center, physician's office, or at home)

dMMRMismatch repair deficient

Revision History

2019revised

2019 Update: Added Keytruda indication for esophageal cancer; Bavencio moved into this policy and new indication for renal cell carcinoma added.

2020revised

2020 Update: Added Tecentriq indication for BRAF V600 mutation-positive unresectable or metastatic melanoma in combination with cobimetinib and vemurafenib.

2021revised

Policy Summary

PayerPremera Bluecross

PolicyMEDICAL POLICY 5.01.591 Immune Checkpoint Inhibitors

Policy CodePolicy 5.01.591

Change TypeIndication additions, removals, SOS criteria, coding updates

Effective DateOct 3, 2025

Next Review DateN/A

Key ActionObtain required site-of-service and medical-necessity reviews and submit medical records documenting diagnosis, history, exam and medication history when requesting coverage.

On This Page

preferred medically necessary site for specified drugs

Home infusion

considered medically necessary for IV infusion and injection therapy when appropriate and contracted home infusion available

Hospital-based outpatient setting

considered medically necessary for initial course or re-initiation after ≥6 months; or when no outpatient infusion center within 50 miles or no contracted home infusion agency will travel; or when clinical condition increases risk of complications

Clinical conditions making hospital-based outpatient setting medically necessary

Known cardiac condition (e.g., symptomatic cardiac arrhythmia) or pulmonary condition (e.g., significant respiratory disease; serious obstructive airway disease; %FVC < 40%) that may increase risk of adverse reaction
Unstable renal function which decreases ability to respond to fluids
Difficult or unstable vascular access
Acute mental status changes or cognitive conditions that impact safety of infusion or injection therapy
Known history of severe adverse drug reactions and/or anaphylaxis to prior treatment with a related or similar drug

Cytokine Release Syndrome (CRS) criteria for inpatient admission

CRS signs: Temperature at least 38°C
CRS signs: Hypotension that requires one or more vasopressors
CRS signs: Hypoxia that requires oxygen via high-flow nasal cannula; face mask; non-rebreather mask; Venturi mask OR positive pressure (CPAP, BiPAP, intubation, or mechanical ventilation)

If CRS grade 3 or 4 documented, arrange inpatient admission promptly

Exception: hospital-based outpatient site may be considered only when above criteria met

Drug-specific medical necessity (examples included in this part)

Each drug may be considered medically necessary when listed age, diagnosis, combination therapy, biomarker testing, and prior treatment requirements are met.

CTLA-4 inhibitor Imjudo (tremelimumab-actl): Imjudo may be considered medically necessary when ALL: individual is aged 18+ AND (has unresectable HCC to be used with Imfinzi OR has metastatic NSCLC with no sensitizing EGFR/ALK aberrations to be used with Imfinzi)

CTLA-4 inhibitor Yervoy (ipilimumab): Yervoy may be considered medically necessary for any of: treatment of unresectable/metastatic melanoma (≥12 yrs), adjuvant melanoma with nodal involvement after resection, intermediate/poor-risk advanced RCC with Opdivo, MSI-H/dMMR unresectable/metastatic colorectal cancer with Opdivo, single-agent for brain metastases if active against primary tumor, first-line or subsequent HCC when with Opdivo per indications

PD-1 inhibitor Jemperli (dostarlimab-gxly): Jemperli may be considered medically necessary when ALL: individual is aged 18+ AND meets one of: primary advanced or recurrent endometrial cancer in combination with carboplatin+paclitaxel; recurrent/advanced endometrial cancer that is dMMR; recurrent/advanced solid tumors that are dMMR and progressed with no satisfactory alternative. FDA-approved dMMR testing required for some Jemperli indications before coverage determination.

FDA-approved dMMR testing required for some indications

PD-1 inhibitor Keytruda (pembrolizumab): Keytruda may be considered medically necessary for indications including unresectable/metastatic melanoma; adjuvant Stage IIB/IIC/III melanoma (≥12 yrs); multiple NSCLC indications (eg, first-line single agent for PD-L1 TPS ≥50% with no EGFR/ALK/ROS1 mutations; combination with pemetrexed+platinum for non-squamous when no EGFR/ALK/ROS1 aberrations or while awaiting results); and multiple other tumor-specific indications per label. FDA-approved testing for PD-L1, EGFR/ALK/ROS1, or TMB-H required before coverage for certain Keytruda indications.

PD-1 inhibitor Libtayo (cemiplimab): Libtayo may be considered medically necessary for metastatic or locally advanced cutaneous squamous cell carcinoma not candidates for curative surgery/radiation; locally advanced/metastatic basal cell carcinoma previously treated with or not appropriate for hedgehog inhibitor; locally advanced/metastatic NSCLC with high PD-L1 (TPS >50%) as single agent first-line without EGFR/ALK/ROS1; NSCLC in combination with platinum chemo per indications.

PD-1 inhibitor Loqtorzi (toripalimab-tpzi): Loqtorzi may be considered medically necessary for adults with metastatic or recurrent locally advanced nasopharyngeal carcinoma (NPC) in combination with cisplatin and gemcitabine.

PD-1 inhibitor Opdivo (nivolumab) and combinations: Opdivo may be considered medically necessary for multiple indications including adjuvant Stage IIB–IV melanoma (≥12 yrs), unresectable/metastatic melanoma (including combinations with Yervoy), resectable NSCLC (≥4 cm or node positive) as neoadjuvant with platinum-doublet followed by adjuvant nivolumab, metastatic NSCLC with PD-L1 and no EGFR/ALK/ROS1 per listed combinations, and other tumor-specific indications per label.

Opdivo Qvantig (SC nivolumab + hyaluronidase): Opdivo Qvantig may be considered medically necessary per listed indications including first-line unresectable advanced/metastatic ESCC in combination with Yervoy for PD-L1 ≥1% and other indications mirroring IV nivolumab; subject to site-of-service review except when used concurrently with other infusion/injection cancer meds.

PD-1 inhibitor Tevimbra (tislelizumab-jsgr): Tevimbra may be considered medically necessary for first-line adults with unresectable/metastatic ESCC with PD-L1 ≥1% when used with platinum chemo; other indications mirroring listed uses per label including gastric/GEJ indications.

Opdualag (nivolumab + relatlimab): Opdualag may be considered medically necessary for adult and pediatric individuals ≥12 years with unresectable or metastatic melanoma.

PD-L1 inhibitor Bavencio (avelumab): Bavencio may be considered medically necessary for metastatic Merkel cell carcinoma (≥12 yrs), maintenance treatment of locally advanced/metastatic urothelial carcinoma not progressed after first-line platinum chemo, urothelial carcinoma with progression during/after platinum chemo or within 12 months of neoadjuvant/adjuvant platinum, and first-line advanced RCC in combination with axitinib per label.

PD-L1 inhibitor Imfinzi (durvalumab): Imfinzi may be considered medically necessary when ALL: individual aged 18+ AND meets one of multiple listed indications including resectable NSCLC (>4 cm and/or node positive) as neoadjuvant with platinum chemo then adjuvant durvalumab; NSCLC progressed following concurrent platinum chemo and radiation; metastatic NSCLC with no EGFR/ALK aberrations when used with Imjudo and platinum chemo; limited-stage SCLC after cCRT as single agent; first-line ES-SCLC with etoposide+carboplatin/cisplatin; biliary tract cancer with gemcitabine+cisplatin; uHCC with Imjudo; primary advanced/recurrent dMMR endometrial cancer with carboplatin+paclitaxel then durvalumab; MIBC with gemcitabine+cisplatin neoadjuvant then adjuvant durvalumab.

subject to site-of-service review except when used concurrently with other infusion/injection medications

PD-1 inhibitor Penpulimab-kcqx: Penpulimab-kcqx may be considered medically necessary for first-line recurrent or metastatic non-keratinizing NPC in combination with cisplatin or carboplatin+gemcitabine, and for metastatic non-keratinizing NPC with progression after platinum-based chemo as single agent.

PD-L1 inhibitor Tecentriq (atezolizumab) and Tecentriq Hybreza (SC): Tecentriq may be considered medically necessary for multiple indications including first-line metastatic NSCLC with high PD-L1 (TC ≥50% or IC ≥10%) with no EGFR/ALK aberrations; first-line metastatic non-squamous NSCLC with bevacizumab+paclitaxel+carboplatin combinations; adjuvant Stage II and IIIA NSCLC with PD-L1 ≥1%; unresectable/metastatic HCC with bevacizumab (adults only); BRAF V600 mutation-positive melanoma with cobimetinib+vemurafenib; ASPS in individuals ≥2 years; and other label indications. Tecentriq Hybreza SC likewise follows listed indications and is subject to site-of-service review except when used concurrently with other infusion/injection meds.

Unloxcyt (cosibelimab-ipdl): Unloxcyt may be considered medically necessary when ALL: individual is aged 18+; is not a candidate for curative surgery or curative radiation; has not received prior anti-PD-1/PD-L1 or other immune checkpoint inhibitor; and is prescribed as monotherapy.

Unloxcyt (cosibelimab-ipdl) - Medical Necessity

Unloxcyt may be considered medically necessary when ALL of the following are met:

Unloxcyt (cosibelimab-ipdl) - Medical Necessity: Individual is aged 18 years or older; is not a candidate for curative surgery or curative radiation; has not received prior treatment with an anti-PD-1/PD-L1 blocking antibody or other immune checkpoint inhibitor; Unloxcyt is prescribed as monotherapy for mCSCC or laCSCC; Dose is limited to 1,200 mg administered every 3 weeks (operational dosing limit)

Operational dosing limit: 1,200 mg every 3 weeks

Zynyz (retifanlimab-dlwr) - Medical Necessity

Zynyz may be considered medically necessary for ALL of the following indications (statements list coverage); no explicit per-patient criteria provided in this part beyond indication/prior therapy constraints:

Covered Indications: Treatment of adult individuals with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC) who may have received surgery or radiation but have not received prior systemic therapy

Covered Indications: First-line treatment of adults with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) when used in combination with carboplatin and paclitaxel

Covered Indications: Treatment of adults with locally recurrent or metastatic SCAC with progression on or intolerance to platinum-based chemotherapy when used as a single agent

General Drug Coverage Rule (multiple agents)

General policy position for listed agents:

General Drug Coverage Rule (multiple agents): Medications listed are subject to the product's FDA dosage and administration prescribing information AND all other uses not listed in this policy are considered investigational

Length of Approval / Authorization

Approval durations described for initial and reauthorization reviews:

Length of Approval / Authorization: Non-formulary exception reviews for all drugs listed in the policy may be approved up to 12 months; all other reviews may be approved (length unspecified in this part); Re-authorization: non-formulary exception and other re-authorizations may be approved up to 12 months if drug-specific coverage criteria are met and chart notes demonstrate continued positive clinical response to therapy

Documentation Requirements

Medical records submitted for review should document that medical necessity criteria are met and include ALL of the following:

Documentation Requirements: Office visit notes that contain the diagnosis, relevant history, physical evaluation and medication history

General coverage posture and updates

Policy includes agent-specific coverage criteria which are updated when FDA-approved indications change; site-of-service review applies for certain products; products are subject to FDA dosing/administration labeling.

General coverage posture and updates: Coverage is provided when treatment aligns with FDA-approved indications and the policy's agent-specific criteria (as updated); site-of-service medical necessity review applies for specified drugs except for Alaska fully-insured members (Alaska HB 226) and may be waived when agent used concurrently with other IV cancer medications; medications must follow product's FDA dosage and administration prescribing information

Agent-specific indication additions and removals (selection of actions reflected in this part)

Policy documents multiple agent-specific coverage additions, clarifications, and removals by date; coverage is updated only for FDA-approved indications and removed when indication withdrawn due to lack of efficacy.

Examples of added indications: Opdivo: first-line advanced RCC with cabozantinib; Opdivo adjuvant and neoadjuvant/resectable NSCLC; Opdivo+Yervoy: first-line for MSI-H/dMMR metastatic CRC; Keytruda: multiple added indications (mesothelioma, cervical cancer, resectable HNSCC, adjuvant NSCLC); Tecentriq Hybreza SC and other additions across years; Imfinzi, Yervoy, Loqtorzi, Zynyz, Tevimbra, Unloxcyt, Jemperli, Imjudo, Opdualag also had additions per history

Examples not exhaustive

Examples of removed indications: Imfinzi: removed urothelial carcinoma coverage (withdrawn for lack of efficacy); Tecentriq: removed several lung/urothelial/TNBC indications withdrawn due to lack of efficacy; Keytruda: removed 3rd-line monotherapy for PD-L1 positive gastric/GEJ cancer when indication withdrawn; Opdivo: removed certain HCC and melanoma indications when FDA removed them

Policy removes coverage when FDA indication withdrawn

Documentation Required

Biomarker testing required prior to coverage

For indications that require a documented biomarker to establish eligibility, FDA-approved testing must be provided before coverage will be determined. Examples include PD-L1 testing, mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H), tumor mutational burden-high (TMB-H), and tumor genomic tests for EGFR, ALK, ROS1 where relevant to therapy selection.

Provide results of FDA-approved companion diagnostic testing when required by the specific drug labeling or indication (e.g., PD-L1 assay for PD-L1–directed indications).
dMMR/MSI-H testing is required prior to coverage for agents indicated for dMMR/MSI-H tumors (e.g., dostarlimab for certain endometrial or solid tumors).
Genomic testing for EGFR, ALK, ROS1 (and other specified alterations) is required when the drug’s indication is limited to tumors without these sensitizing alterations.
Document TMB-H status when relied upon for an indicated approval.
If an FDA-approved companion diagnostic is specified in the FDA label for the indication, that test must be used and results submitted.

Documentation Required

Submit medical records documenting medical necessity

Submit complete medical records to support medical necessity decisions. Records should include documentation of diagnosis, prior therapies, rationale for immune checkpoint inhibitor use, and details of planned administration.

Office visit notes and problem list
History and physical examination
Medication and infusion history, including prior immunotherapy and responses
Pathology and radiology reports supporting diagnosis and staging
Results of required biomarker and genomic testing (see Biomarker testing)
Treatment plan including dosing, schedule, and planned site of service

Documentation Required

CRS inpatient admission criteria

Cytokine release syndrome (CRS) of grade 3–4 requires prompt inpatient admission. Admit patients when CRS meets all of the following clinical criteria and arrange immediate inpatient management.

Grade 3–4 CRS defined by: temperature ≥38°C; hypotension requiring vasopressors; and hypoxia requiring high-flow oxygen delivery (high-flow nasal cannula, non-rebreather, Venturi mask) or positive pressure support (CPAP/BiPAP) or mechanical ventilation.
If CRS meets these criteria, document vital signs, oxygen requirement, vasopressor use, and plan for inpatient admission.
Do not delay admission — inpatient level care should be initiated promptly when grade 3–4 CRS is present.

Documentation Required

Site of service exception documentation

Document exceptions to preferred outpatient sites when requesting hospital-based outpatient administration due to lack of local outpatient infusion availability or inability of home infusion services to travel.

If there is no outpatient infusion center within 50 miles, include documentation of distance and local resources searched.
If no contracted home infusion agency will travel to the patient’s home, include written verification from the home infusion agency.
If hospital is the only provider offering infusion/injection of the specific drug in the region, include supporting documentation.

Prior Authorization

Non-formulary exception and other reviews authorization length

Non-formulary exceptions and other special authorization reviews may be approved for up to 12 months when medically necessary. Reauthorization requires evidence of continued benefit and ongoing medical necessity.

Initial non-formulary or special exception approvals may be granted up to 12 months in duration based on indication and clinical judgment.
Reauthorization requests must include documentation of clinical response, tolerance, and plan for continued therapy.
Shorter authorization periods may be issued when clinical review or safety monitoring is required.

Billing Rule

Report unclassified / NOC J-codes appropriately

Unclassified or not otherwise classified (NOC) oncology J‑codes should be reported per payer instruction when specific HCPCS codes are not assigned. Use C9399 or J9999 as appropriate for reporting unclassified drug administrations and include drug name and NDC on claims.

Report unclassified/NOC J-codes (e.g., C9399, J9999) when no specific HCPCS/J-code exists for the administered product.
Include drug name, dose, NDC, and supporting documentation with the claim when using unclassified codes.
Examples of products that may require NOC coding include recently approved or limited-distribution formulations (e.g., Tecentriq Hybreza, penpulimab-kcqx when a specific code is not available).

Billing Rule

Use specified HCPCS/J-codes for reporting

Use the specified HCPCS/J-codes when available to report checkpoint inhibitor administrations. Report the most specific applicable code and include dose and administration details on the claim.

Commonly used HCPCS/J-codes included in this policy: J9173, J9023, J9119, J9272, J9298, C9147, J9345, J3263, J9329, J9275, J9289, J9999.
When a specific product code exists, do not use NOC codes; report the assigned HCPCS/J-code with dose and NDC information as required.

Documentation Required

Follow FDA dosing and administration

Follow FDA-approved product labeling for dosing, administration, premedication, and monitoring. Deviations from labeled dosing schedules require clinical justification and supporting documentation.

Adhere to dosing, infusion rates, premedication, and monitoring instructions in the FDA label for each agent.
If weight- or body-surface-area-based dosing is used, document calculations and measured weight/BSA in the medical record.
Any off‑label dosing or schedule must be justified in the record with supporting literature or rationale.

Note

Site-of-service review for Keytruda and Opdivo

Keytruda (pembrolizumab) and Opdivo (nivolumab) are subject to site-of-service medical necessity review except when administered concurrently with other IV or injectable cancer therapies. When given with other cancer infusions, SOS review for these agents is not required.

Keytruda and Opdivo are SOS-reviewed agents for site-of-service determinations for members aged ≥13.
If Keytruda or Opdivo are administered concurrently with other IV cancer medications during the same encounter, SOS review is not required for the checkpoint inhibitor.
Document concurrent administration and list accompanying agents and indications when claiming an exception to SOS review.

TMB-HTumor mutational burden-high defined in policy as ≥10 mutations/megabase (mut/Mb) (Keytruda reference)

CRSCytokine Release Syndrome; grading referenced for inpatient admission criteria (grade 3–4 criteria include temp ≥38°C, hypotension requiring vasopressors, hypoxia requiring high-flow O2 or positive pressure)

PD-1Programmed cell death protein 1 (PD-1), a protein on immune cells that down-regulates immune response and is a target for checkpoint inhibitors

PD-L1Programmed death-ligand 1 (PD-L1), a ligand that binds PD-1 and suppresses T-cell activity; target of PD-L1 inhibitors

2022revised

2022 Update: Removed Keytruda as 3rd line monotherapy for PD-L1 positive gastric/GEJ cancer; added site of service review for Keytruda and Opdivo.

2023revised

2022-2025added

Multiple new FDA indications added for agents including Opdivo, Keytruda, Tecentriq Hybreza, Tevimbra, Imfinzi, Yervoy, Unloxcyt and others across 2022-2025.

2022-2025removed

Coverage removed when FDA indications withdrawn for multiple agents (e.g., Imfinzi for urothelial carcinoma; Tecentriq for several withdrawn indications; Keytruda 3rd-line gastric/GEJ).

2025revisedLatest

Site-of-service medical necessity criteria added or expanded to include several additional agents and clarified applicability to injection drugs; Alaska fully-insured members exempted per HB 226.

through 07/2025revisedLatest

Multiple HCPCS/J-code additions and removals reflecting coding updates (examples: added J9275, J9289, J9329, J3263, J9345, J9298, J9272; removed C9082, J3590, J9258).

unspecifiedclarified

Site of Service Medical Necessity criteria applies only to medical benefit reviews and does not apply to Alaska fully-insured members.