Draftblue cross blue shield - tennesseePolicy N/A

Pembrolizumab (Keytruda®)

Defines covered indications, prior-authorization documentation requirements, exclusions, authorization durations (mostly 6 months), and clinical/testing criteria for pembrolizumab across multiple tumor types. Part 1 of 2 contains indications, limitations, documentation and many condition-specific authorization rules.

Policy Summary

Payerblue cross blue shield - tennessee

PolicyPembrolizumab (Keytruda®)

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateID_CHS_2026a

Next Review Date

Key ActionProvider must submit prior authorization with required documentation including PD-L1, MSI/MMR/POLE/POLD1 status and TMB reports, receptor status (HER2/ER/PR) and EGFR/ALK/RET/ROS1 testing as applicable.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this update.

30+Covered Indications (FDA + compendial listed)

40+Indications listed

6 monthsTypical Authorization Duration

24 monthsMaximum reauthorization continuous use for some indications

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Explicit Exclusions (examples)

Coverage Summary & Scope

This policy covers pembrolizumab (Keytruda®) for FDA‑approved tumor‑specific indications, recognized compendial uses, and biomarker‑driven tumor‑agnostic approvals (notably MSI‑H/dMMR and TMB‑H). Coverage is provided when all indication‑specific approval criteria and required documentation are met and the member has no listed exclusions. Part 1 of 2 describes covered indications, limitations, required documentation for prior authorization, exclusions, typical authorization durations (commonly 6 months), and many condition‑specific rules and limits.

General Coverage Condition

Coverage is provided for FDA-approved indications and compendial uses provided all approval criteria are met and member has no exclusions to therapy.

Indication is FDA-approved or listed compendial use in the policy
All approval criteria specific to the indication are met
Member does not have any listed exclusions to pembrolizumab

Initial Therapy Criteria & Prior Authorization Requirements

Documentation Required for Prior Authorization

Documentation Required for Prior Authorization (submit ALL applicable items):

all

Prior Authorization

Prior Authorization Required

Prior authorization is required for pembrolizumab (Keytruda®) for covered indications; approvals are typically granted for an initial period (commonly 6 months) consistent with diagnosis‑specific dosing limits. Provide complete clinical and biomarker documentation to avoid delays.

PD-L1 test report where the indication requires PD-L1 expression (report CPS or TPS and assay used)
MSI/MMR testing report (IHC or PCR) or POLE/POLD1 results when applicable
Tumor mutational burden (TMB) report with numeric result and test method (threshold: TMB ≥ 10 mut/Mb where applicable)
Receptor status reports (e.g., HER2, ER, PR) for indications requiring receptor testing
EGFR, ALK, RET, ROS1 testing results for NSCLC and other indications where required

Continuation Therapy / Reauthorization Criteria

Billing Rule

Authorization Duration & Dosing Compliance

Authorizations are generally issued for 6 months; some indications allow longer reauthorization (up to 12 or 24 months) when the member has not experienced disease progression or unacceptable toxicity.

Dosing must follow the diagnosis-specific maximum regimens listed in the policy
Pediatric weight-based dosing limits (e.g., 2 mg/kg up to 200 mg) apply

Unproven / Exclusions (Not Covered)

Indication-Specific Criteria (Examples Consolidated)

Authorization Duration and Indication-Specific Criteria (examples consolidated)

Cutaneous Melanoma
- Unresectable or metastatic disease as a single agent.
- Subsequent therapy for metastatic or unresectable disease, as single agent or in combination with ipilimumab or lenvatinib.
- Neoadjuvant treatment as a single agent.
- Adjuvant treatment following complete lymph node resection or complete resection of stage IIB, IIC, III, or metastatic disease as a single agent.

Medication Quantity Limits & Dosing by Diagnosis

Dosing is administered intravenously unless otherwise noted, and maximum dosing regimens vary by diagnosis (examples include 200 mg every 3 weeks or 400 mg every 6 weeks for many adult indications). Pediatric dosing uses weight‑based regimens (e.g., 2 mg/kg every 3 weeks up to 200 mg) where specified.

Medication quantity limits and dosing by diagnosis

Maximum dosing regimens specified by diagnosis (route intravenous unless noted):

Ampullary Adenocarcinoma: 200 mg every 3 weeks or 400 mg every 6 weeks.
Anal Carcinoma: 200 mg every 3 weeks; 400 mg every 6 weeks; 2 mg/kg every 3 weeks; 4 mg/kg every 6 weeks.
Biliary Tract Cancer: 200 mg every 3 weeks.

Applicable Codes

No codes listed in Part 1mixed

No codes listed

Definitions & Clinical Thresholds

TMB‑H: Tumor mutational burden‑high, defined here as ≥10 mutations/megabase (mut/Mb) (except ultra‑hypermutated phenotype defined as >50 mut/Mb where specified).

MSI‑H/dMMR: Microsatellite instability‑high (MSI‑H) or mismatch repair deficient (dMMR) as determined by an FDA‑approved test.

CPS: Combined Positive Score (PD‑L1) — PD‑L1 tumor expression scoring used where indicated (e.g., CPS ≥1 or CPS ≥10 depending on indication).

Clinical Evidence & References

Primary reference: Keytruda [package insert], Merck; February 2026.

This policy aligns coverage to FDA approvals and recognized compendia (e.g., NCCN) and follows those approvals and guidance when applying indication‑specific criteria and documentation requirements.

Provider Actions & Documentation Checklist

Prior Authorization

Submit Prior Authorization

Request prior authorization for pembrolizumab for covered indications.

Prior authorizations are typically granted for 6 months
Longer reauthorization windows (e.g., up to 12 or 24 months) apply for specified indications when no progression or unacceptable toxicity

Documentation Required

Documentation Checklist

Include laboratory and pathology reports that confirm biomarker and mutation status required to support approval.

PD-L1 (TPS or CPS)
MSI‑H / dMMR (including POLE/POLD1 where applicable)
Tumor Mutational Burden (TMB ≥10 mut/Mb)
HER2 / ER / PR status
EGFR / ALK / RET / ROS1 testing

Background

Pembrolizumab is an anti–PD‑1 monoclonal antibody with multiple tumor‑specific FDA indications and tumor‑agnostic approvals for MSI‑H/dMMR and TMB‑H (≥10 mut/Mb) solid tumors. The policy aligns coverage to FDA‑approved indications, compendial uses, and biomarker‑driven criteria and requires documentation (e.g., PD‑L1, MSI/MMR, TMB reports) to support prior authorization.

Revision History

Policy Summary

Payerblue cross blue shield - tennessee

PolicyPembrolizumab (Keytruda®)

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateID_CHS_2026a

Next Review Date

SourceLink

On This Page

Requested pembrolizumab dosing regimen and calculation demonstrating it matches the diagnosis-specific dose/schedule limits

Documentation Required

Required Laboratory/Pathology Evidence

Include laboratory and pathology reports that confirm biomarker status and other diagnostic findings relevant to the indication. Submit actual test reports (not summaries) showing numeric scores, assay names, and interpretation.

PD-L1: assay name, numeric result and interpretation (TPS or CPS as applicable)
MSI-H / dMMR: method and result (IHC, PCR, or NGS-based report)
TMB: numeric result with units (mutations/megabase) and method; note threshold of ≥ 10 mut/Mb for TMB-H indication
HER2 / ER / PR: pathology/immunohistochemistry and scoring reports for breast/gastric indications
EGFR / ALK / RET / ROS1: molecular testing reports for NSCLC and other tumor types where targeted alterations affect eligibility
Any additional tumor sequencing or biomarker reports (e.g., POLE, POLD1) when cited in the indication

Subsequent or re-induction therapy in combination with trametinib and dabrafenib for metastatic/unresectable disease with a BRAF V600 activating mutation.

Non-Small Cell Lung Cancer (NSCLC)

No EGFR exon 19 deletions or exon 21 L858R mutations or ALK, RET or ROS1 gene fusions/rearrangements (unless testing not feasible due to insufficient tissue).
Single agent first-line therapy for PD-L1 positive disease.PD-L1 TPS >=1%
Single agent or in combination with pemetrexed for maintenance therapy.
Combination with pemetrexed and carboplatin or cisplatin for nonsquamous histology.
Combination with carboplatin and paclitaxel or albumin-bound paclitaxel for squamous histology.

Head and Neck Cancer (HNSCC)

Resectable stage III-IVa non-nasopharyngeal HNSCC with PD-L1 CPS ≥1 when used as single-agent neoadjuvant, continued as adjuvant with RT ± cisplatin and then as single agent.PD-L1 CPS >=1
Very advanced HNSCC or nasopharyngeal cancer: single agent first-line if PD-L1 CPS ≥1, or MSI-H/dMMR or TMB-H (≥10 mut/Mb); or single agent subsequent therapy; or in combination with cetuximab or chemotherapy.TMB >=10 mut/Mb

Classical Hodgkin Lymphoma

Relapsed or refractory cHL: single agent; in combination with GVD; in combination with ICE; or with decitabine or vorinostat if refractory to ≥3 prior lines.

Urothelial Carcinoma

First-line therapy for stage II, recurrent, locally advanced or metastatic bladder urothelial carcinoma in members ineligible for any platinum-containing chemotherapy.
Subsequent therapy for stage II, recurrent, locally advanced or metastatic disease.
Adjuvant therapy.

Solid Tumors (tumor-agnostic)

Unresectable or metastatic solid tumors progressed following prior treatment with no satisfactory alternatives when tumor is MSI-H or dMMR.
Tumor mutational burden-high (≥10 mut/Mb) solid tumors.>= 10 mut/Mb

Bone Cancer: 200 mg every 3 weeks or 400 mg every 6 weeks.

Breast Cancer: 200 mg every 3 weeks or 400 mg every 6 weeks.

Cervical Cancer: 200 mg every 3 weeks or 400 mg every 6 weeks.

Classical Hodgkin Lymphoma (cHL): ≥18 years: 200 mg every 3 weeks or 400 mg every 6 weeks; <18 years: 2 mg/kg every 3 weeks (up to 200 mg).

CNS Cancer (brain metastases): 200 mg every 3 weeks or 400 mg every 6 weeks.

Colorectal Cancer: 200 mg every 3 weeks; 400 mg every 6 weeks; 2 mg/kg every 3 weeks.

Cutaneous Squamous Cell Carcinoma: 200 mg every 3 weeks or 400 mg every 6 weeks.

Endometrial Carcinoma: 200 mg every 3 weeks or 400 mg every 6 weeks.

Esophageal/Gastric/GEJ Cancer: 200 mg every 3 weeks or 400 mg every 6 weeks.

Head and Neck Squamous Cell Carcinoma: 200 mg every 3 weeks or 400 mg every 6 weeks.

Hepatocellular Carcinoma: 200 mg every 3 weeks.

Kaposi Sarcoma: 200 mg every 3 weeks.

Mesothelioma: 200 mg every 3 weeks or 400 mg every 6 weeks.

Melanoma: 200 mg every 3 weeks or 400 mg every 6 weeks.

Pediatric Melanoma (Adjuvant): ≥12 to <18 years: 2 mg/kg every 3 weeks (up to 200 mg).

Merkel Cell Carcinoma: 200 mg every 3 weeks or 400 mg every 6 weeks; <18 years: 2 mg/kg every 3 weeks (up to 200 mg).

MSI-H/dMMR Cancer: ≥18 years: 200 mg every 3 weeks or 400 mg every 6 weeks; <18 years: 2 mg/kg every 3 weeks (up to 200 mg).

NSCLC or SCLC: 200 mg every 3 weeks or 400 mg every 6 weeks.

Pediatric Diffuse High-Grade Gliomas: <18 years: 200 mg every 3 weeks; adult regimens 400 mg every 6 weeks listed.

Primary Mediastinal Large B-cell Lymphoma: 200 mg every 3 weeks or 400 mg every 6 weeks; <18 years: 2 mg/kg every 3 weeks (up to 200 mg).

Tumor Mutational Burden-High Cancer: ≥18 years: 200 mg every 3 weeks or 400 mg every 6 weeks; <18 years: 2 mg/kg every 3 weeks (up to 200 mg).

Urothelial/Bladder/Upper GU/Urethra: 200 mg every 3 weeks or 400 mg every 6 weeks.

Billing Rule

Dosing Regimens Must Match Diagnosis‑Specific Limits

Adhere to the listed maximum dosing regimens by diagnosis and pediatric weight-based limits when administering pembrolizumab.

Billing Rule

Authorization & Billing Rules

Authorizations are typically for 6 months and dosing must adhere to diagnosis-specific limits when billing.

Reauthorization may be extended up to 12 months for some adjuvant indications and up to 24 months for other specified indications when no progression/toxicity
Pediatric dosing constraints (weight‑based; e.g., 2 mg/kg up to 200 mg) must be followed