CurrentNeighborhood Health Plan of Rhode IslandPolicy 1889-A SGM P2024b

Keytruda Indications Document

Defines covered FDA-approved and compendial indications for pembrolizumab (Keytruda), documentation required for prior authorization, exclusions, initial authorization criteria (mostly 6-month approvals by indication), and reauthorization rules including duration limits and conditions.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyKeytruda Indications Document

Policy CodePolicy 1889-A SGM P2024b

Change TypeNo material changes

Effective DateJan 1, 2024

Next Review Date

Key ActionPrior authorization is required; submit documentation of PD-L1, MSI-H/dMMR, TMB (≥10 mut/Mb) and relevant receptor and EGFR/ALK testing when applicable.

POLICY UPDATE CHANGES

No material clinical or coverage changes in this policy update.

24FDA-approved or compendial major disease categories listed

6 monthsTypical initial authorization duration

≥10 mut/MbTMB-H threshold used

Up to 24 monthsReauthorization continuous use for many indications

Coverage Summary & Indications

This policy defines coverage for FDA‑approved and compendial indications for pembrolizumab (Keytruda), requires submission of specified clinical and biomarker documentation for prior authorization (including PD‑L1, MSI‑H/dMMR, and TMB ≥ 10 mut/Mb where applicable), lists exclusions (for example, pediatric TMB‑H CNS cancers and progression on prior PD‑1/PD‑L1 therapy with a limited melanoma exception), and typically authorizes initial treatment for 6 months with defined reauthorization duration limits (some adjuvant uses up to 12 months total and many indications up to 24 months continuous use).

Compendial Uses (covered)

The following compendial uses are considered covered when approval criteria are met:

ANY of the following

Cutaneous melanoma
Non-small cell lung cancer
Head and neck squamous cell cancer
Classical Hodgkin Lymphoma
Urothelial carcinoma (including bladder, urethra, upper GU tract, prostate urothelial carcinoma)
Anaplastic thyroid carcinoma
Follicular, Oncocytic (Hürthle cell), or papillary thyroid carcinoma
Medullary thyroid carcinoma
Colorectal cancer
Small bowel adenocarcinoma
Gastric and esophagogastric junction cancer
Esophageal cancer
Cervical cancer
Epithelial ovarian/fallopian tube/primary peritoneal cancer
Uveal melanoma
Testicular cancer
Endometrial carcinoma
Anal carcinoma
CNS brain metastases
Primary mediastinal large B-cell lymphoma
Pancreatic adenocarcinoma
Biliary tract cancers
Vulvar cancer
Renal cell carcinoma
Thymic carcinoma
Primary cutaneous lymphomas (Mycosis Fungoides/Sezary syndrome; relapsed/refractory ALCL)
Extranodal NK/T-cell lymphoma
Gestational trophoblastic neoplasia
Neuroendocrine and adrenal tumors (including well-differentiated grade 3; adrenal gland; extrapulmonary poorly differentiated)
Soft tissue sarcomas (ASPS, cutaneous angiosarcoma, extremity/body wall, head/neck, retroperitoneal/intra-abdominal, rhabdomyosarcoma)
Occult primary cancer
Prostate cancer
Bone cancers (chondrosarcoma, chordoma, Ewing, osteosarcoma)
Breast cancer
Salivary gland tumors
Merkel cell carcinoma
Penile cancer
Uterine sarcoma
Small cell lung cancer
Ampullary adenocarcinoma
Pediatric diffuse high-grade gliomas
Cutaneous squamous cell carcinoma
Nasopharyngeal cancer
Kaposi sarcoma

Prior Authorization & Documentation Requirements

Prior Authorization

Prior authorization required

Prior authorization is required. Submit documentation of PD-L1 tumor expression where applicable; laboratory reports confirming MSI-H or dMMR tumor status where applicable; laboratory report confirming tumor mutational burden (TMB) (≥10 mut/Mb) where applicable; laboratory report confirming that cancer cells are negative for HER-2, estrogen, and progesterone receptors where applicable (e.g., TNBC); and documentation of presence/absence of EGFR exon 19 deletions or L858R mutations or ALK rearrangements where applicable.

PD-L1 tumor expression (when applicable)
Laboratory report: MSI-H or dMMR (when applicable)
Laboratory report: TMB ≥10 mut/Mb (when applicable)
Laboratory report: HER-2, estrogen, progesterone receptor negativity (when applicable)
Documentation of EGFR exon 19 deletions / L858R or ALK rearrangements (when applicable)

Documentation Required

Biomarker test reports required

Provide laboratory reports with the prior authorization submission as indicated by the requested indication: PD-L1 testing results (TPS or CPS as applicable); laboratory report confirming MSI-H or dMMR tumor status where applicable; laboratory report confirming high tumor mutational burden (TMB-H, ≥10 mut/Mb) where applicable; receptor testing showing HER-2, estrogen, and progesterone status (negative required for triple-negative breast cancer) where applicable; and documentation of EGFR exon 19 deletions or L858R mutations or ALK rearrangements where applicable.

PD-L1 (TPS or CPS as applicable)
MSI-H or dMMR laboratory report
TMB (≥10 mut/Mb) laboratory report
Receptor status: HER-2, estrogen, progesterone (as applicable; required negative for TNBC)
EGFR/ALK mutation testing where applicable

Billing Rule

Initial authorization duration

Initial authorizations are typically granted for 6 months for covered indications. Note: some adjuvant indications may allow reauthorization up to 12 months total (e.g., adjuvant melanoma, high-risk early-stage TNBC, RCC, NSCLC), and selected indication groups may be reauthorized for up to 24 months of continuous use (e.g., NSCLC, HNSCC, cHL, PMBCL, MSI-H/dMMR cancers, gastric, esophageal, cervical, HCC, MCC, RCC, endometrial carcinoma, cSCC, locally recurrent unresectable/metastatic TNBC, TMB-H, biliary tract cancers).

Typical initial authorization: 6 months
Adjuvant groups: reauthorization up to 12 months total
Selected groups: reauthorization up to 24 months continuous use

Denial Risk

Exclusion - prior PD-1/PD-L1 progression

Coverage is excluded for members who experienced disease progression while on a PD-1 or PD-L1 inhibitor. Exception: second-line or subsequent therapy for metastatic or unresectable melanoma in combination with ipilimumab following progression on single-agent anti–PD-1 immunotherapy is allowed.

Exclude members with disease progression on PD-1/PD-L1 therapy
Melanoma exception: combination with ipilimumab after progression on single-agent anti–PD-1 permitted

Reauthorization Criteria & Duration Limits

Reauthorization criteria and duration limits

Conditions for continued treatment and maximum continuous use durations by indication group:

ANY of the following

Adjuvant melanoma, high-risk early-stage TNBC, RCC, NSCLC (adjuvant)
- Authorization 6 months may be granted (up to 12 months total) for continued treatment if member has not experienced disease recurrence or unacceptable toxicityup to 12 months total
NSCLC, HNSCC, cHL, PMBCL, MSI-H/dMMR cancers, gastric, esophageal, cervical, HCC, MCC, RCC, endometrial carcinoma, cSCC, locally recurrent unresectable/metastatic TNBC, TMB-H, biliary tract cancers
- Authorization 6 months may be granted (up to 24 months continuous use) for continued treatment if member has not experienced disease progression or unacceptable toxicityup to 24 months continuous use
Urothelial carcinoma (with enfortumab vedotin-ejfv)
- Authorization 6 months may be granted for continued treatment if no progression or unacceptable toxicity
- High-risk BCG-unresponsive NMIBC only: authorization 6 months (up to 24 months continuous use) if disease is not persistent or recurrent and no unacceptable toxicityup to 24 months continuous use for high-risk BCG-unresponsive NMIBC
All other indications listed in Section IV
- Authorization 6 months may be granted for continued treatment if member has not experienced disease progression or unacceptable toxicity

Required Documentation for Prior Authorization

Documentation required for prior authorization

Submission of the following is necessary to initiate prior authorization review where applicable:

ALL of the following

PD-L1 tumor expression: Documentation of PD-L1 tumor expression, where applicable
MSI-H or dMMR: Laboratory report confirming MSI-H or dMMR tumor status, where applicable
TMB: Laboratory report confirming high tumor mutational burden (≥10 mut/Mb), where applicable≥10 mut/Mb
Receptor status for TNBC: Laboratory report confirming that cancer cells are negative for HER-2, estrogen, and progesterone receptors, where applicable
EGFR/ALK status: Documentation of presence/absence of EGFR exon 19 deletions or L858R mutations or ALK rearrangements, where applicable

Key numeric biomarker and staging thresholds

PD-L1 TPS threshold≥1% (required for certain NSCLC single-agent indications)

PD-L1 CPS thresholdsCPS ≥1 or CPS ≥10 depending on indication (e.g., HNSCC CPS ≥1; esophageal squamous CPS ≥10; cervical CPS ≥1; TNBC CPS ≥10)

TMB-H threshold≥10 mutations per megabase (mut/Mb)

MSI-H / dMMRPositive by an FDA‑approved test (MSI‑H or dMMR) where applicable

NSCLC neoadjuvant tumor size cutoffResectable tumors ≥4 cm or node positive (eligible for neoadjuvant pembrolizumab + platinum chemo)

NSCLC adjuvant stage cutoffsAdjuvant single‑agent after resection + platinum chemo for stage IB (T2a ≥4 cm), stage II, or stage IIIA

Background & Definitions

This policy background references the Keytruda package insert (January 2024) and the NCCN Drugs & Biologics Compendium (accessed February 19, 2024) and focuses on listing FDA‑approved and compendial indications and the prior authorization documentation and biomarker requirements needed to evaluate coverage requests.

PD‑L1 TPS: Tumor Proportion Score — the percentage of tumor cells with PD‑L1 expression (used where indicated).

PD‑L1 CPS: Combined Positive Score — PD‑L1 expression in tumor and immune cells as determined by an FDA‑approved test (used where indicated).

MSI‑H: Microsatellite instability‑high as determined by an FDA‑approved test (biomarker for eligibility where indicated).

dMMR: Mismatch repair deficient as determined by an FDA‑approved test (biomarker for eligibility where indicated).

TMB‑H: Tumor mutational burden‑high defined as ≥10 mutations/megabase (mut/Mb) (as determined by an FDA‑approved test; note pediatric CNS TMB‑H safety/effectiveness not established).

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyKeytruda Indications Document

Policy CodePolicy 1889-A SGM P2024b

Change TypeNo material changes

Effective DateJan 1, 2024

Next Review Date

Key ActionPrior authorization is required; submit documentation of PD-L1, MSI-H/dMMR, TMB (≥10 mut/Mb) and relevant receptor and EGFR/ALK testing when applicable.

On This Page

OpenPayer

Keytruda Indications Document

Coverage Summary & Indications

Prior Authorization & Documentation Requirements

Initial Authorization by Indication

Reauthorization Criteria & Duration Limits

Not Covered / Exclusions

Required Documentation for Prior Authorization

Policy Identifiers & Codes

References & Evidence Sources

Background & Definitions

Policy Dates & Revision History

1889-A	Keytruda reference number / policy identifier
1889-A SGM P2024b	Policy number (document header)