CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Pembrolizumab (Keytruda) — Coverage Criteria

Defines covered FDA and compendial indications for pembrolizumab (Keytruda) and the authorization/coverage criteria and documentation requirements for members of Neighborhood Health Plan of Rhode Island.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyPembrolizumab (Keytruda) — Coverage Criteria

Policy CodePolicy N/A

Change TypeNo material change

Effective Date

Next Review Date

Key ActionSubmit prior authorization with documentation of required tumor biomarkers (e.g., MSI‑H/dMMR, TMB‑H ≥10 mut/Mb, PD‑L1) and prior therapies as applicable.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

40+listed FDA and compendial indications or tumor types

6 monthstypical authorization period

TMB-H ≥10TMB threshold cited

TPS/CPSPD-L1 biomarker required (examples)

MSI‑H / dMMRMSI‑H / dMMR indications

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Covered Indications and Criteria

Cutaneous Melanoma

Covered when ANY of the following are met:

Melanoma settings: Authorization of 6 months may be granted for unresectable, recurrent, or metastatic cutaneous melanoma as a single agent; as subsequent therapy for progression (single agent or in combination with ipilimumab); or as adjuvant treatment following complete lymph node resection or resection of stage IIB, IIC, III, or metastatic disease.

Non‑Small Cell Lung Cancer (NSCLC)

Covered when ALL required conditions per subsetting are met:

First-line PDL1+ NSCLC: Requested medication used as first-line therapy for PD-L1 positive disease with no EGFR exon 19 deletions/L858R mutations or ALK rearrangements (unless testing not feasible due to insufficient tissue). May be used as single-agent maintenance or in combination regimens depending on histology (with carboplatin + paclitaxel or albumin-bound paclitaxel for squamous; with pemetrexed + platinum for nonsquamous).

Authorization of 6 months may be granted.

Adjuvant or subsequent: Authorization of 6 months may be granted as single-agent adjuvant treatment following resection and platinum-based chemotherapy for stage IB (T2a ≥4 cm), II, or IIIA; or as single-agent subsequent treatment of PD-L1 positive recurrent/advanced/metastatic NSCLC after progression on platinum-containing chemotherapy (with prior targeted therapy required for EGFR/ALK aberrations if applicable).

Head and Neck Squamous Cell Carcinoma (HNSCC)

Covered when ANY of the following are met:

First-line PD-L1+ or biomarker-high HNSCC: Pembrolizumab as a single agent for first-line treatment in tumors that express PD-L1 (CPS ≥1), or that are MSI-H, dMMR, or TMB-H (≥10 mut/Mb).

Authorization of 6 months may be granted.

Subsequent or combination therapy: Authorization of 6 months may be granted for single-agent subsequent therapy regardless of PD-L1 status, or when used in combination with chemotherapy regardless of PD-L1 status.

Classical Hodgkin Lymphoma

Covered when ALL of the following are met:

cHL relapsed/refractory: Authorization of 6 months may be granted for relapsed, refractory, or progressive classical Hodgkin lymphoma when pembrolizumab is requested as a single agent or in combination with GVD (gemcitabine, vinorelbine, liposomal doxorubicin).

Urothelial / Bladder Cancer

Covered when ANY of the following are met:

First-line platinum-ineligible: Pembrolizumab used as first-line therapy for locally advanced or metastatic urothelial carcinoma in members who are not eligible for any platinum-containing chemotherapy.

Authorization of 6 months may be granted as single agent.

Subsequent therapy or high-risk NMIBC: Authorization of 6 months may be granted as a single agent for subsequent therapy; and for BCG-unresponsive high-risk non-muscle invasive bladder cancer (CIS) when the member is ineligible for or has elected not to undergo cystectomy and disease meets BCG-unresponsive criteria.

Biomarker-driven and other indications

Biomarker-driven and other indications — covered when documented biomarker status and approval criteria are met:

MSI-H/dMMR tumors: Pembrolizumab is indicated for unresectable or metastatic MSI-H or dMMR solid tumors; laboratory documentation confirming MSI-H or dMMR is required.

Authorization of 6 months may be granted as single agent when prior treatment has failed and no satisfactory alternative exists.

TMB-H tumors: Pembrolizumab is indicated for unresectable or metastatic tumor mutational burden-high (TMB-H) solid tumors with TMB ≥10 mut/Mb; laboratory documentation confirming TMB-H is required.>= 10 mut/Mb

Authorization of 6 months may be granted as single agent when prior treatment has failed and no satisfactory alternative exists.

Other FDA/compendial indications: Numerous additional tumor types (for example: gastric, esophageal, cervical, hepatocellular, Merkel cell carcinoma, renal cell carcinoma, endometrial, TNBC, PMBCL, pancreatic, ampullary, ovarian, testicular, anal, and others) are covered per FDA or compendial indications when the specific approval criteria and required documentation are met.

Classical Hodgkin Lymphoma

Covered when ALL of the following are met:

Classical Hodgkin Lymphoma: Authorization of 6 months may be granted as a single agent or in combination with GVD (gemcitabine, vinorelbine, liposomal doxorubicin) for relapsed, refractory or progressive classical Hodgkin lymphoma.

Urothelial Carcinoma / Bladder Cancer

Covered when ONE of the following applies:

Bladder Urothelial Carcinoma: First-line for locally advanced/metastatic disease in members ineligible for any platinum-containing chemotherapy; OR subsequent therapy; OR for high-risk BCG-unresponsive NMIBC with CIS when member is ineligible for or declines cystectomy.

Authorization of 6 months as single agent.

Urothelial Carcinoma (urethra/upper GU/ prostate)

Covered when ONE of the following applies:

Primary Urethra / Upper GU Urothelial: First-line for recurrent, locally advanced, or metastatic disease in members who are not eligible for any platinum-containing chemotherapy; OR subsequent therapy for recurrent or metastatic disease.

Authorization of 6 months as single agent.

Biomarker-defined Solid Tumors (MSI-H/dMMR, TMB-H)

Covered when ANY of the following biomarker conditions are met for unresectable/metastatic solid tumors after prior treatment:

Biomarker-driven solid tumors: MSI-H/dMMR solid tumors; OR tumor mutational burden-high (TMB-H ≥10 mut/Mb) solid tumors.MSI-H or TMB-H >=10 mut/Mb

Authorization of 6 months as single agent when no satisfactory alternative options exist.

Anaplastic Thyroid Carcinoma

Covered when ALL of the following are met:

Anaplastic Thyroid Carcinoma: Metastatic anaplastic thyroid carcinoma with tumor mutational burden-high (TMB-H ≥10 mut/Mb).TMB-H >=10 mut/Mb

Authorization of 6 months as single agent.

Thyroid Carcinomas (various histologies)

Covered when ALL of the following are met:

Follicular/Hurthle/Papillary Thyroid Carcinoma: Unresectable or metastatic follicular, hurthle cell, or papillary thyroid carcinoma not amenable to radioactive iodine with tumor mutational burden-high (TMB-H ≥10 mut/Mb).TMB-H >=10 mut/Mb

Authorization of 6 months.

Medullary Thyroid Carcinoma: Unresectable, recurrent, or metastatic medullary thyroid carcinoma with tumor mutational burden-high (TMB-H ≥10 mut/Mb).TMB-H >=10 mut/Mb

Authorization of 6 months.

Gastrointestinal Tumors (colorectal, small bowel, gastric, esophageal)

Covered when ANY of the following biomarker or disease conditions are met:

Colorectal Cancer: Inoperable, advanced, or mismatch repair deficient (dMMR/MSI-H) colorectal tumors (authorization of 6 months).dMMR/MSI-H

Small Bowel Adenocarcinoma: Advanced/metastatic small bowel adenocarcinoma that is MSI-H/dMMR (authorization of 6 months).MSI-H/dMMR

Gastric Cancer: Subsequent single-agent therapy for MSI-H/dMMR or TMB-H tumors; also combination regimens for HER2-overexpressing disease as specified (authorization of 6 months when unresectable or metastatic).MSI-H/dMMR or TMB-H

Other tumor-specific authorizations

Other tumor-specific authorizations — covered when indication-specific conditions are met:

Merkel Cell Carcinoma: Recurrent or metastatic Merkel cell carcinoma (authorization of 6 months).

Uveal Melanoma: Distant metastatic uveal melanoma (authorization of 6 months).

Testicular Cancer: Third-line therapy for testicular cancer in members with MSI-H/dMMR or TMB-H tumors (authorization of 6 months).MSI-H/dMMR or TMB-H

Anal Carcinoma: Subsequent single-agent treatment of metastatic anal carcinoma (authorization of 6 months).

Reference 1889-A.

Endometrial Carcinoma

Covered when ALL of the following are met:

Endometrial Carcinoma (pMMR): Requested drug used in combination with lenvatinib; member has disease progression following prior systemic therapy; and member is not a candidate for curative surgery or radiation.pMMR

Authorization of 6 months.

Endometrial Carcinoma (MSI-H): Single-agent authorization of 6 months for recurrent unresectable or metastatic MSI-H tumors.MSI-H/dMMR

CNS Brain Metastases

Authorization of 6 months may be granted as a single agent for CNS brain metastases when one of the following tumor types is present:

CNS brain metastases tumor types: Member has melanoma OR PD-L1 positive non-small cell lung cancer.

From chunk 36

Primary Mediastinal Large B-Cell Lymphoma

Authorization of 6 months may be granted when ALL required conditions are met:

Primary Mediastinal LBCL: Relapsed or refractory primary mediastinal large B-cell lymphoma; pembrolizumab as single agent or in combination with brentuximab vedotin.

From chunk 37

Pancreatic Adenocarcinoma

Authorization of 6 months may be granted when biomarker or clinical settings are met:

Pancreatic adenocarcinoma biomarker settings: Tumors that are MSI-H OR dMMR OR TMB-H (≥10 mut/Mb).TMB-H >=10 mut/Mb

From chunk 38

Pancreatic adenocarcinoma clinical settings: Local recurrence in the pancreatic operative bed after resection OR recurrent metastatic disease OR first-line or maintenance therapy for metastatic disease.

From chunk 38

Hepatobiliary Cancers

Authorization of 6 months may be granted when ALL of the following are met:

Hepatobiliary cancers: Unresectable or metastatic intrahepatic or extrahepatic cholangiocarcinoma or gallbladder cancer with MSI-H or dMMR.

From chunk 39

Hepatocellular Carcinoma

Authorization of 6 months may be granted when ALL of the following are met:

Hepatocellular carcinoma: Member previously treated with sorafenib (prior systemic therapy).

From chunk 40

Vulvar Cancer

Authorization of 6 months may be granted when ANY of the following are met:

Vulvar cancer biomarker or prior therapy: MSI-H OR dMMR OR TMB-H; OR disease progression on or after chemotherapy with tumor PD-L1 CPS >1.

From chunk 41

Renal Cell Carcinoma

Authorization of 6 months may be granted when ANY of the specified regimen/setting criteria are met:

RCC coverage options: First-line in combination with axitinib or lenvatinib for advanced/relapsed/stage IV disease; OR subsequent therapy in combination with axitinib or lenvatinib for relapsed/stage IV clear cell histology; OR single agent for relapsed or stage IV non-clear cell histology; OR single-agent adjuvant therapy for intermediate-high or high risk post-nephrectomy.

From chunk 42

Thymic Carcinoma

Authorization of 6 months may be granted when ALL of the following are met:

Thymic carcinoma: Unresectable, locally advanced, or metastatic thymic carcinoma; or postoperative residual tumor when the member cannot tolerate first-line combination regimens.

From chunk 43

Primary Cutaneous Lymphomas

Authorization of 6 months may be granted when ANY of the following diagnoses are present:

Primary cutaneous lymphomas: Mycosis fungoides/Sezary syndrome OR relapsed/refractory anaplastic large cell lymphoma (ALCL) when pembrolizumab is used as a single agent.

From chunk 44

Extranodal NK/T-cell Lymphoma

Authorization of 6 months may be granted when ALL of the following are met:

Extranodal NK/T-cell lymphoma: Relapsed or refractory extranodal NK/T-cell lymphoma.

From chunk 45

Gestational Trophoblastic Neoplasia

Authorization of 6 months may be granted when ANY of the following are met:

Gestational trophoblastic neoplasia: Recurrent or progressive intermediate trophoblastic tumor following a platinum–etoposide-containing regimen OR high-risk gestational trophoblastic disease.

From chunk 46

Neuroendocrine and Adrenal Tumors

Authorization of 6 months may be granted when ALL of the following are met:

Adrenocortical carcinoma: Unresectable or metastatic adrenocortical carcinoma.

From chunk 47

Cutaneous Squamous Cell Carcinoma

Authorization of 6 months may be granted when ALL of the following are met:

Cutaneous squamous cell carcinoma that is not curable by surgery or radiation.

From chunk 48

Soft Tissue Sarcoma

Authorization of 6 months may be granted when ANY of the following are met:

Soft tissue sarcoma coverage: Pembrolizumab used as single agent or with axitinib for alveolar soft part sarcoma (ASPS) OR single agent for cutaneous angiosarcoma.

From chunk 49

Occult Primary Cancer

Authorization of 6 months may be granted when ANY of the following biomarker conditions are met:

Occult primary cancer biomarkers: MSI-H OR dMMR OR TMB-H (≥10 mut/Mb) in occult primary cancers.TMB-H >=10 mut/Mb

From chunk 50

Breast Cancer (TNBC)

Authorization statements for triple-negative breast cancer — covered when ALL required conditions are met:

TNBC metastatic/unresectable: Confirmed triple-negative breast cancer (negative for HER2, estrogen receptor, and progesterone receptor) AND tumor must express PD-L1; used in combination with chemotherapy for locally recurrent unresectable or metastatic disease (authorization of 6 months).

TNBC high-risk early-stage: Confirmed triple-negative breast cancer AND used as neoadjuvant in combination with chemotherapy or continued as single-agent adjuvant therapy after surgery (authorization of 6 months, per criteria).

Prostate Cancer

Authorization of 6 months may be granted when ANY of the following are met:

Prostate cancer: Castration-resistant distant metastatic prostate cancer as single-agent subsequent therapy in members with MSI-H, dMMR, or TMB-H (≥10 mut/Mb) tumors; OR single-agent subsequent therapy for relapsed or progressive disease.TMB-H >=10 mut/Mb

From chunk 52

Pediatric Diffuse High-Grade Gliomas

Authorization of 6 months may be granted when ANY of the following are met:

Pediatric diffuse high-grade glioma: Hypermutant pediatric diffuse high-grade glioma as adjuvant treatment, or for recurrent/progressive disease.

From chunk 53

Ampullary Adenocarcinoma

Authorization of 6 months may be granted when ANY of the following biomarker conditions are met:

Ampullary adenocarcinoma biomarkers: MSI-H OR dMMR OR TMB-H (≥10 mut/Mb) ampullary adenocarcinoma.TMB-H >=10 mut/Mb

From chunk 54

Kaposi Sarcoma

Authorization of 6 months may be granted when ALL required conditions are met:

Kaposi Sarcoma: Subsequent treatment for relapsed/refractory endemic or classic Kaposi sarcoma as a single agent.

From chunk 55

Continuation/Reauthorization — adjuvant and advanced indications

Continuation/Reauthorization — covered for continued treatment when ALL of the following are met:

Adjuvant indications continued treatment: Member requesting reauthorization for adjuvant treatment of cutaneous melanoma, high-risk early-stage TNBC, RCC, or NSCLC who has not experienced disease recurrence or unacceptable toxicity.no disease recurrence or unacceptable toxicity

Authorization of 6 months may be granted (up to 12 months total)

Multiple advanced/metastatic indications continued treatment: Member requesting reauthorization for NSCLC, HNSCC, cHL, PMBCL, MSI-H or dMMR cancers, gastric, esophageal, cervical, HCC, MCC, RCC, endometrial carcinoma, cutaneous SCC, locally recurrent unresectable or metastatic TNBC, and TMB-H cancers who have not experienced disease progression or unacceptable toxicity.no disease progression or unacceptable toxicity

Authorization of 6 months may be granted (up to 24 months of continuous use)

Continuation/Reauthorization — urothelial carcinoma

Continuation/Reauthorization — covered for continued treatment when ALL of the following are met:

Urothelial carcinoma reauthorization: Member has not experienced disease progression or unacceptable toxicity. For high-risk BCG-unresponsive non-muscle invasive bladder cancer only: disease is not persistent or recurrent.authorization of 6 months may be granted (up to 24 months of continuous use)

Other specific indications and general reauthorization

Other specific indications and general reauthorization — covered for continued treatment when ALL of the following are met:

Ampullary adenocarcinoma (biomarker-driven): Single-agent pembrolizumab may be authorized for MSI-H, dMMR, or TMB-H (≥10 mut/Mb) ampullary adenocarcinoma for continued treatment.authorization of 6 months

From chunks 54 and 58

Kaposi Sarcoma subsequent treatment: Single-agent pembrolizumab may be authorized for subsequent treatment of relapsed/refractory endemic or classic Kaposi sarcoma.authorization of 6 months

From chunk 55

General reauthorization for listed indications: Members requesting reauthorization for an indication listed in Section IV who have not experienced disease progression or unacceptable toxicity.

Coverage is excluded for pediatric members with central nervous system (CNS) tumors that are MSI-H or TMB-H. In addition, requests will be denied for members who experienced disease progression while receiving a PD‑1 or PD‑L1 inhibitor, except for the specific melanoma scenario described in the policy (second‑line or subsequent therapy for metastatic or unresectable melanoma in combination with ipilimumab following progression on single‑agent anti‑PD‑1 therapy).

For BCG‑unresponsive high‑risk non‑muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), pembrolizumab eligibility requires that the member be ineligible for or have elected not to undergo cystectomy. Cases that do not meet the BCG‑unresponsive definition or where the member is a candidate for cystectomy do not qualify under this pathway.

Authorization for cutaneous squamous cell carcinoma is limited to disease that is not curable by surgery or radiation. Tumors that are amenable to definitive surgery or radiation should not be authorized for pembrolizumab under this indication.

Reauthorization will not be granted if the member has experienced disease progression or unacceptable toxicity. For urothelial carcinoma reauthorizations, the member must have no disease progression or unacceptable toxicity; for high‑risk BCG‑unresponsive NMIBC specifically, continued authorization also requires that the disease is not persistent or recurrent.

Use of pembrolizumab for indications that are not listed as FDA‑approved or supported by recognized compendia in the policy is considered experimental/investigational and not medically necessary and therefore not eligible for coverage.

When authorization depends on biomarker status, use in tumors lacking the required marker (for example, MSI‑H/dMMR or TMB‑H ≥10 mut/Mb) is unsupported by the criteria and will not meet medical necessity requirements. Laboratory documentation confirming the specified biomarker is required for these indications.

Permitted Regimens and Combinations

Regimen	Indication / Histology	Coverage status
Pembrolizumab + carboplatin + paclitaxel or paclitaxel protein-bound
First-line treatment of metastatic squamous NSCLC
Pembrolizumab + pemetrexed + platinum (carboplatin or cisplatin)
First-line treatment of metastatic nonsquamous NSCLC (no EGFR/ALK aberrations)
Pembrolizumab + platinum + fluorouracil
First-line treatment for applicable head and neck squamous cell carcinoma regimens where indicated

Regimen	Indication / Setting	Coverage status
Pembrolizumab + lenvatinib
First-line treatment of advanced renal cell carcinoma
Pembrolizumab + axitinib
First-line treatment of advanced renal cell carcinoma

Regimen	Indication	Coverage status
Pembrolizumab (single agent)
Relapsed, refractory, or progressive classical Hodgkin lymphoma
Pembrolizumab in combination with GVD (gemcitabine, vinorelbine, liposomal doxorubicin)
Relapsed, refractory, or progressive classical Hodgkin lymphoma

Regimen	Required conditions	Coverage status
Pembrolizumab + lenvatinib
pMMR endometrial carcinoma after disease progression following prior systemic therapy; member not a candidate for curative surgery or radiation

Regimen	Indication / Setting	Coverage status
Pembrolizumab (single agent)
Relapsed or refractory primary mediastinal large B-cell lymphoma
Pembrolizumab + brentuximab vedotin
Relapsed or refractory primary mediastinal large B-cell lymphoma

Regimen	Indication / Setting	Coverage status
Pembrolizumab + axitinib
First-line treatment for advanced/relapsed/stage IV renal cell carcinoma
Pembrolizumab + lenvatinib
First-line treatment for advanced/relapsed/stage IV renal cell carcinoma
Pembrolizumab (single agent)
Adjuvant single-agent for intermediate-high or high risk post-nephrectomy; or single agent for relapsed or stage IV non-clear cell histology

Regimen	Indication / Setting	Coverage status
Pembrolizumab (single agent)
Relapsed or refractory primary mediastinal large B-cell lymphoma
Pembrolizumab + brentuximab vedotin
Relapsed or refractory primary mediastinal large B-cell lymphoma

Regimen	Indication	Coverage status
Pembrolizumab (single agent)
Alveolar soft part sarcoma (ASPS)
Pembrolizumab + axitinib
Alveolar soft part sarcoma (ASPS)

Authorization, Documentation, and Denial Triggers

Prior Authorization

Prior Authorization Required

Prior authorization is required for treatment with pembrolizumab (Keytruda) for the indications listed in this policy. Typical initial and continuation authorizations are granted for up to 6 months; select indications and reauthorization scenarios allow extensions (see reauthorization callouts).

Authorization length: standard 6 months for most listed indications.
Some authorizations may be extended per reauthorization criteria (see continuation/reauthorization guidance).

Denial Risk

Biomarker-Dependent Denials Possible

Requests lacking documented tumor biomarker status when required by the indication (for example MSI-H/dMMR, PD‑L1 expression, or TMB‑H) may be denied. Ensure laboratory/pathology reports demonstrating the specific biomarker result requested are included.

Common biomarker dependencies: MSI‑H/dMMR, PD‑L1 (CPS or percent as specified), TMB‑H (≥10 mut/Mb).
If testing is not feasible (e.g., insufficient tissue), note this and include supporting documentation.

Denial Risk

Progression or Toxicity Triggers Denial

Requests for continued therapy (reauthorization) will be denied if the member has experienced disease progression or unacceptable toxicity on pembrolizumab for the applicable indication. Reauthorization must document ongoing benefit and absence of progression or unacceptable adverse effects.

Reauthorization denial triggers: documented disease progression while on therapy or unacceptable toxicity.
For urothelial carcinoma and other listed indications, reauthorization requires evidence the member has not progressed and is tolerating therapy.

Documentation Required

Required Documentation for Prior Authorization

Submit the following documentation to initiate prior authorization review. Incomplete submissions may delay review or result in denial.

Laboratory or pathology report confirming MSI‑H or dMMR status where applicable.
Laboratory or pathology report documenting PD‑L1 tumor expression where applicable (include CPS or percentage as reported).
Laboratory report confirming TMB result where applicable (TMB‑H defined as ≥10 mut/Mb).
Receptor testing reports where required (e.g., HER‑2, estrogen, progesterone negative results to confirm TNBC).
Documentation of presence or absence of EGFR exon 19 deletions, L858R mutations, or ALK rearrangements for NSCLC when applicable.
Detailed prior therapy history, including prior chemotherapy, targeted therapies, and exposure to platinum agents where cited.

Documentation Required

Required Clinical Documentation

Clinical documentation must include the tumor biomarker status and a clear prior therapy history supporting the requested use. Where the indication requires prior systemic therapy or prior specific agents, provide treatment dates and responses.

Evidence of prior systemic therapy and disease progression when the indication specifies prior treatment (e.g., endometrial carcinoma pMMR after prior systemic therapy).
For indications requiring prior platinum exposure or prior sorafenib (HCC), include records showing prior treatment and dates.
For NSCLC, document absence of actionable EGFR/ALK alterations when required or provide reason testing was not feasible.

Documentation Required

Required Reauthorization Documentation

For reauthorization requests, submit documentation demonstrating the member has not experienced disease progression and has not had unacceptable toxicity while on therapy. Some adjuvant and other indications have maximum continuous use limits—provide treatment start dates to support duration limits.

Reauthorization requirements: evidence of no progression and no unacceptable toxicity.
Adjuvant therapy: reauthorization may be granted in 6‑month increments up to indication-specific total duration limits (e.g., up to 12 months total for some adjuvant uses; up to 24 months for many continuing indications).
Urothelial carcinoma (high‑risk BCG‑unresponsive NMIBC): for reauthorization, disease must not be persistent or recurrent and member must not have progressed.

Prior Authorization

Prior Therapy Required for HCC

For hepatocellular carcinoma (HCC), prior treatment with sorafenib (or documentation of prior systemic therapy per the indication) must be provided to support authorization.

Include records showing prior sorafenib treatment and dates or documentation of prior systemic therapy for HCC.
Authorization is typically granted for 6 months when prior sorafenib therapy is documented.

Biomarker Thresholds and Documentation Expectations

TMB — threshold used in policy

TMB threshold>= 10 mutations per megabase (mut/Mb)

Source wording noteDocument lists TMB-H as '210 mutationslmegabase' or '210 mutationslmegabase [mut/Mb]' which is interpreted as ≥10 mut/Mb in policy statements

Required documentationLaboratory report confirming high tumor mutational burden required for prior authorization when applicable

PD-L1 (TPS or CPS) — indication-specific thresholds cited

PD-L1 metrics usedPD-L1 expression reported as Tumor Proportion Score (TPS) or Combined Positive Score (CPS) depending on indication

Examples of TPS useNSCLC indications reference PD-L1 TPS (e.g., TPS ≥1% for first-line/single-agent and TPS thresholds for other NSCLC settings)

Examples of CPS useCervical, esophageal, and TNBC indications reference PD-L1 CPS thresholds (e.g., CPS ≥1 or CPS ≥10 as cited per tumor type)

MSI-H / dMMR — biomarker designation referenced

Biomarker designationMSI-H = microsatellite instability-high; dMMR = mismatch repair deficient

Indication examplesMSI-H/dMMR tumors are listed as covered indications for endometrial, colorectal, pancreatic, hepatobiliary, occult primary, and other solid tumors

Documentation requiredLaboratory report confirming MSI-H or dMMR status required for prior authorization when applicable

EGFR / ALK — biomarker mention for exclusion/selection

EGFR / ALK considerationNSCLC use as single-agent first-line or subsequent therapy requires absence of EGFR exon 19 deletions/L858R and ALK rearrangements (unless testing not feasible)

Documentation notePresence of EGFR exon 19 deletions/L858R or ALK rearrangements should be documented where applicable

ImplicationPatients with these genomic alterations should receive appropriate targeted therapy prior to Keytruda where specified

TMB (tumor mutational burden) — interpreted as >= 10 mutations/megabase

Interpreted threshold>= 10 mutations/megabase (mut/Mb) for TMB-H

Policy text examplesPancreatic adenocarcinoma and ampullary adenocarcinoma sections explicitly reference TMB-H ≥10 mut/Mb (written as 'z 10 mutlMb' in source)

Authorization implicationTMB-H (≥10 mut/Mb) supports single-agent pembrolizumab authorization for unresectable/metastatic tumors when other criteria met

MSI-H / dMMR — biomarker designation repeated

MSI-H definitionMSI-H (microsatellite instability-high) listed as an eligible biomarker for multiple tumor types (e.g., endometrial, colorectal, ovarian)

dMMR equivalencedMMR (mismatch repair deficient) is presented interchangeably with MSI-H for coverage determinations

Required evidencePrior authorization requires lab report confirming MSI-H or dMMR status when applicable

PD-L1 (CPS) — CPS thresholds cited

CPS thresholds citedPD-L1 Combined Positive Score (CPS) thresholds referenced as indication-specific (examples include CPS ≥1 and CPS ≥10)

Tumor examplesCervical and esophageal cancer sections specifically cite PD-L1 CPS thresholds for single-agent or combination use

DocumentationLaboratory report confirming PD-L1 expression (CPS) required for prior authorization when applicable

TMB — >=10 mut/Mb referenced in multiple sections

Repeated threshold>= 10 mut/Mb repeatedly referenced across multiple tumor-specific sections

Sections citing TMB-HSolid tumors, pancreatic adenocarcinoma, ampullary adenocarcinoma, and others reference TMB-H (policy shows formatting variants)

Prior auth implicationRequests lacking evidence of TMB-H where required may be unsupported and denied

MSI-H / dMMR — repeated biomarker references

MSI-H/dMMR presenceMSI-H or dMMR listed repeatedly as qualifying biomarkers for multiple tumor types (solid tumors, pancreatic, hepatobiliary, occult primary)

Equivalence notePolicy treats MSI-H and dMMR as equivalent determinants of eligibility in cited indications

Documentation requirementLaboratory confirmation of MSI-H or dMMR is necessary for prior authorization when applicable

PD-L1 — CPS >1 for vulvar cancer and other PD-L1 mentions

Vulvar cancer CPS mentionVulvar cancer subsequent-treatment pathway references tumor PD-L1 CPS > 1 as a criterion

Other PD-L1 mentionsPD-L1 expression also referenced for CNS brain metastases (PD-L1+ NSCLC) and TNBC (tumor must express PD-L1)

DocumentationPD-L1 expression reports required for indications that cite PD-L1 thresholds

MSI-H — biomarker mention in reauthorization and indications

MSI-H in reauthorizationMSI-H/dMMR cancers are included among indications eligible for reauthorization when no progression or unacceptable toxicity is documented

Adjuvant vs advancedMSI-H single-agent pathways appear in both initial authorization and continued treatment lists (authorization durations specified)

Required evidence for reauthReauthorization requires documentation of no disease progression or unacceptable toxicity

dMMR — biomarker mention in reauthorization and indications

dMMR in reauthorizationdMMR-listed cancers are eligible for continued treatment reauthorization when criteria (no progression/toxicity) are met

Overlap with MSI-HPolicy lists MSI-H and dMMR together across initial and reauthorization sections

Documentation for reauthLab confirmation of dMMR required when applicable for prior authorization and reauthorization requests

TMB-H — explicit text 'TMB-H z 10 mutlMb' interpreted as ≥ 10 mut/Mb

Explicit TMB-H textPolicy text includes 'TMB-H z 10 mutlMb' which is interpreted as TMB-H ≥ 10 mut/Mb

Indication examplesAmpullary adenocarcinoma and pancreatic adenocarcinoma sections explicitly reference this TMB-H notation

Authorization implicationTMB-H meeting this threshold supports single-agent pembrolizumab authorization when other criteria are met

Permitted Lines of Therapy

first-line | second-line | subsequent — 2 top-level nodes

First-line: Indication as first-line therapy per tumor-specific combination or single-agent approvals (examples include NSCLC histology-directed combinations and TPS/CPS-directed single-agent uses).

Top-level line-of-therapy node.

Second-line/subsequent: Indication as subsequent or maintenance therapy per tumor-specific approvals (examples include single-agent subsequent therapies after platinum-containing chemotherapy).

Top-level line-of-therapy node.

first-line | second-line | third-line — 1 top-level node

Line examples: Line-of-therapy examples include first-line options for platinum-ineligible members, subsequent therapy for recurrent/metastatic disease, and third-line use (e.g., testicular cancer).

Single top-level node representing first/second/third-line groupings.

subsequent therapy — 1 top-level node

Subsequent therapy examples: Subsequent therapy criteria include prior systemic therapy requirements where specified (for example, hepatocellular carcinoma previously treated with sorafenib; prostate cancer subsequent therapy in mCRPC).

Single top-level node representing subsequent therapy.

first-line | adjuvant | neoadjuvant — 1 top-level node

First-line | adjuvant | neoadjuvant: Examples include TNBC: neoadjuvant in combination with chemotherapy, continued adjuvant single-agent use after surgery, and first-line metastatic settings when combined with chemotherapy per PD-L1 status.

Single top-level node.

Key Biomarker and Test Codes / Thresholds

Tumor Mutational Burden (TMB) — >= 10 mutations/megabase

TMB numeric threshold>= 10 mutations/megabase (mut/Mb)

Policy appearanceTMB threshold appears in coding, definitions, biomarker, and tumor-specific sections across the document

Prior auth noteLaboratory confirmation of high TMB required for requests relying on TMB-H eligibility

PD-L1 expression thresholds — TPS and CPS thresholds used per indication

PD-L1 thresholds overviewPD-L1 expression thresholds are cited as TPS or CPS and are applied per indication (e.g., NSCLC, HNSCC, TNBC, cervical, esophageal)

TPS exampleNSCLC sections reference PD-L1 Tumor Proportion Score (TPS) thresholds for single-agent and other uses

CPS exampleCervical, esophageal, and TNBC sections reference PD-L1 Combined Positive Score (CPS) thresholds (e.g., CPS ≥1 or CPS ≥10)

Tumor mutational burden — interpreted as >= 10 mutations/megabase

TMB repeated interpretation>= 10 mutations/megabase (document formatting variants indicate the same threshold)

Sections referencing TMBSolid tumors, thyroid, pancreatic, ampullary, ovarian, testicular and other tumor sections reference TMB-H at this level

Coding alignmentCoding thresholds list TMB-H as >=10 mut/Mb for use in prior authorization and coverage decisions

PD-L1 CPS — CPS ≥1 or CPS ≥10 depending on indication

PD-L1 CPS thresholdsCPS ≥1 or CPS ≥10 are cited depending on tumor type and indication (examples: cervical CPS ≥1; esophageal CPS ≥10)

Indication-specific applicationCPS thresholds determine eligibility for single-agent or combination therapy in cited tumor types

Documentation requirementPD-L1 CPS must be reported by an FDA-approved test and included with prior authorization when applicable

Tumor Mutational Burden — >= 10 mut/Mb referenced

TMB references>= 10 mut/Mb consistently referenced across tumor-specific criteria

Source formatting noteSource shows variants like '210 mutationslmegabase' but intent across text aligns to ≥10 mut/Mb

Use in coverage decisionsTMB-H at this threshold supports single-agent pembrolizumab authorization for unresectable/metastatic tumors when other criteria are met

TMB threshold — TMB-H ≥ 10 mut/Mb

TMB-H definitionTMB-H ≥ 10 mut/Mb (documented in policy text as 'TMB-H z 10 mutlMb')

Example indicationsAmpullary and pancreatic adenocarcinoma sections explicitly cite this TMB-H notation

Laboratory confirmationPrior authorization requires lab report confirming TMB-H when used to support coverage

Background and Definitions

Pembrolizumab (Keytruda) is an anti–PD‑1 immune checkpoint inhibitor with multiple FDA‑approved oncology indications, including cutaneous melanoma, various lung cancers, head and neck cancer, classical Hodgkin lymphoma, urothelial carcinoma, and biomarker‑defined tumors such as MSI‑H/dMMR and TMB‑H cancers. Coverage in this policy aligns with those FDA‑approved and compendial indications when the specified clinical criteria and documentation requirements are met.

Definition — Tumor mutational burden-high (TMB-H)

Definition (concise)Tumor mutational burden-high (TMB-H) defined as ≥10 mutations per megabase (mut/Mb)

Policy usageTMB-H designation is used to identify solid tumors eligible for pembrolizumab when other criteria are met

Documentation requiredLaboratory report confirming high TMB required for prior authorization when applicable

Definition — PD-L1 expression metrics (TPS and CPS)

PD-L1 metrics explainedPD-L1 expression is reported using Tumor Proportion Score (TPS) or Combined Positive Score (CPS) depending on indication

Clinical applicationTPS used in NSCLC; CPS used in HNSCC, cervical, esophageal, and TNBC examples

Testing requirementPD-L1 must be determined by an FDA-approved test and submitted with prior authorization when applicable

Definition — TMB-H reiterated

TMB-H reiteratedTMB-H repeatedly stated across tumor-specific sections as the biomarker threshold used to determine eligibility

ExamplesThyroid, pancreatic, ovarian, testicular and other tumor sections reference TMB-H

Policy interpretation noteFormatting inconsistencies in source are interpreted to mean ≥10 mut/Mb consistently

Definition — MSI-H / dMMR explained

MSI-H / dMMR explanationMSI-H (microsatellite instability-high) and dMMR (mismatch repair deficient) are biomarker designations used to identify eligible cancers for pembrolizumab

Common indicationsListed for endometrial, colorectal, pancreatic, hepatobiliary, ovarian, and occult primary cancers among others

Documentation requirementLaboratory confirmation of MSI-H or dMMR required for prior authorization when applicable

Definition — PD-L1 CPS explained

PD-L1 CPS explainedCombined Positive Score (CPS) is used to report PD-L1 expression for specific tumor types with indication-specific cutoffs (e.g., CPS ≥1, CPS ≥10)

Tumor examplesCervical cancer and esophageal squamous cell carcinoma use CPS thresholds to determine eligibility for single-agent or combination therapy

Testing requirementPD-L1 CPS must be measured by an FDA-approved test and provided with prior authorization when applicable

Definition — TMB-H referenced across indications

TMB-H across indications>=10 mut/Mb used consistently across multiple indication statements to identify eligible tumors

Policy consistencyDespite formatting differences in source text, the practical threshold is applied uniformly in coverage decisions

Prior auth evidenceLaboratory report confirming TMB-H required when relied upon for coverage

Definition — MSI-H / dMMR / TMB-H biomarker designations

Biomarker groupMSI-H, dMMR, and TMB-H are grouped as biomarker designations that may confer eligibility for pembrolizumab across tumor types

Examples of useThese biomarkers appear together in solid tumor, pancreatic, ampullary, ovarian, and other sections as qualifying criteria

DocumentationLab confirmation of the relevant biomarker is required for prior authorization when applicable

Definition — High-risk BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) subtype

NMIBC subtype definedHigh-risk BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with CIS is a specified subtype eligible for pembrolizumab when member is ineligible for or declines cystectomy

Reauthorization conditionFor this NMIBC subtype, reauthorization requires disease not be persistent or recurrent

Authorization durationInitial or continued authorization of 6 months may be granted for this indication per policy

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyPembrolizumab (Keytruda) — Coverage Criteria

Policy CodePolicy N/A

Change TypeNo material change

Effective Date

Next Review Date

Key ActionSubmit prior authorization with documentation of required tumor biomarkers (e.g., MSI‑H/dMMR, TMB‑H ≥10 mut/Mb, PD‑L1) and prior therapies as applicable.

SourceLink

On This Page

Authorization of 6 months may be granted where specified.

Esophageal/EGJ Cancer: Subsequent single-agent therapy for MSI-H/dMMR or TMB-H tumors; PD-L1 CPS ≥10 applies for some squamous histologies as indicated (authorization of 6 months).MSI-H/dMMR or PD-L1 CPS thresholds

CNS Brain Metastases: Treatment of CNS brain metastases in members with melanoma or PD-L1 positive non-small cell lung cancer (authorization of 6 months).PD-L1 positive for NSCLC

Primary Mediastinal Large B-Cell Lymphoma: Relapsed or refractory PMBCL as single agent or in combination with brentuximab vedotin (authorization of 6 months).

authorization of 6 months