CurrentCapital BluecrossPolicy MP 2.364

Somatic Genetic Testing to Select Individuals with Melanoma or Glioma for Targeted Therapy or Immunotherapy

Policy MP 2.364 defines medical necessity criteria for somatic genetic testing of BRAF V600 variants and NTRK gene fusions to select individuals with melanoma or glioma for FDA‑approved targeted therapies or immunotherapy; it also lists investigational uses and contains coding guidance.

Policy Summary

PayerCapital Bluecross

PolicySomatic Genetic Testing to Select Individuals with Melanoma or Glioma for Targeted Therapy or Immunotherapy

Policy CodePolicy MP 2.364

Change TypeClinical and administrative updates (NTRK criteriacoding changes)

Effective DateSep 1, 2025

Next Review Date

Key ActionProvider must document that testing is being requested to select individuals with unresectable/metastatic melanoma, resected stage III melanoma, or glioma for specific FDA-approved targeted therapy (e.g., BRAF inhibitors/MEK inhibitors, dabrafenib+trametinib for BRAF V600E, or FDA-approved NTRK kinase inhibitors).

SourceLink

POLICY UPDATE CHANGES

06/12/2025 Administrative Update removed Benefit Variations Section and updated Disclaimer.

11/19/2024 Added criteria for NTRK gene fusion testing to select targeted treatment; revised BRAF testing in cutaneous melanoma to include tissue or liquid biopsy; added codes 81191-81194 and 0473U.

04/11/2024 Administrative Update moved immunotherapy indications to MP 2.388 and removed TMB criteria from this policy; CPT 81210 removed and moved to MP 2.388.

11/07/2023 Minor Review: BRAF V600 testing for glioma changed from investigational to medically necessary for BRAF V600E to select dabrafenib+trametinib.

06/12/2024 New code 0473U added effective 07/01/2024.

BRAF V600 coveredMelanoma covered indications

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Glioma covered indication

NTRK fusion coveredNTRK covered indications

TMB investigationalTumor Mutational Burden

Coverage Summary

Policy MP 2.364 addresses somatic genetic testing for BRAF V600 variants and NTRK gene fusions to select individuals with melanoma or glioma for FDA‑approved targeted therapies or immunotherapy. The policy is effective 2025-09-01 and the last review was 2025-06-12. It defines medically necessary indications (e.g., unresectable/metastatic melanoma, resected stage III melanoma for BRAF testing; BRAF V600E in glioma to select dabrafenib+trametinib; NTRK fusion testing for unresectable/metastatic melanoma and glioma) and lists investigational uses (including TMB testing moved to a separate policy). The stance is mixed, with key covered themes focused on selecting patients for specific FDA‑approved targeted agents and investigational themes noting insufficient evidence for other uses.

Policy metadata and quick notes

policy_numberMP 2.364

effective_date2025-09-01

last_review2025-06-12

statusCURRENT

scope_summaryDefines medical necessity criteria for somatic testing of BRAF V600 variants and NTRK fusions to select individuals with melanoma or glioma for FDA‑approved targeted therapies; lists investigational uses and coding guidance.

Medical-Necessity Criteria

Medically Necessary - BRAF V600 testing for melanoma

Testing is considered medically necessary when criteria below are met:

ONE of

Individuals with unresectable or metastatic melanoma
Testing to select individuals for treatment with FDA-approved BRAF inhibitors or MEK inhibitors; see Policy Guidelines
Individuals with resected stage III melanoma
Testing to select individuals for adjuvant treatment with FDA-approved BRAF/MEK inhibitors

Not medically necessary / Investigational - BRAF V600 testing for melanoma

Testing is considered investigational when ALL of the following are met:

ALL of the following

Coding

Covered when medically necessary - Procedure / CPT / Proprietary codesmixedCovered

0473U	Proprietary molecular diagnostic procedure code listed in policy
81191	Oncology (somatic) gene panel or variant testing (listed in policy)
81192	Oncology (somatic) gene panel or variant testing (listed in policy)
81193	Oncology (somatic) gene panel or variant testing (listed in policy)
81194	Oncology (somatic) gene panel or variant testing (listed in policy)
81210	BRAF (v-raf murine sarcoma viral oncogene homolog B1) (note: moved to MP 2.388 per 04/11/2024 update)

Investigational / Not covered (TMB-related code)mixedNot Covered

0037U

Procedure code used for tumor mutational burden (TMB) - investigational per policy

Covered ICD-10 diagnoses (melanoma, glioma)ICD-10Covered

C43.0	Malignant melanoma of lip
C43.10	Malignant melanoma of unspecified eyelid, including canthus
C43.111	Malignant melanoma of right upper eyelid, including canthus
C43.112	Malignant melanoma of right lower eyelid, including canthus
C43.121	Malignant melanoma of left upper eyelid, including canthus
C43.122	Malignant melanoma of left lower eyelid, including canthus
C43.20	Malignant melanoma of unspecified ear and external auricular canal
C43.21	Malignant melanoma of right ear and external auricular canal
C43.22	Malignant melanoma of left ear and external auricular canal
C43.30	Malignant melanoma of unspecified part of face

1–10 of 34

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Provider Actions & Billing Guidance

Documentation Required

Document clinical indication and intent of testing

Provider must document that testing is being requested to select individuals with unresectable/metastatic melanoma, resected stage III melanoma, or glioma for specific FDA‑approved targeted therapy (for example, BRAF inhibitors/MEK inhibitors, dabrafenib+trametinib for BRAF V600E, or FDA‑approved NTRK kinase inhibitors).

Specify the tumor type and stage (e.g., unresectable/metastatic melanoma, resected stage III melanoma, glioma).
State the targeted therapy being considered (e.g., dabrafenib+trametinib, vemurafenib, larotrectinib, entrectinib).
Indicate whether testing is for tissue or liquid biopsy when applicable.

Note

Refer to related policies for tests not listed

If coverage of a test is requested but the test or code is not listed in this policy, refer to MP 2.259 (Expanded Molecular Panel Testing) and MP 2.388 (Somatic Biomarker Testing for Immune Checkpoint Inhibitor Therapy) for guidance on expanded panels or biomarkers related to immunotherapy.

Background and Evidence Context

Background: The policy explains that BRAF variants drive constitutive kinase activity in the RAF‑MEK‑ERK pathway and that BRAF and MEK inhibitors were developed initially for advanced melanoma; identification of these targetable variants guides targeted therapy in melanoma and glioma. It cites FDA approvals and NCCN recommendations supporting use of BRAF and MEK inhibitors in melanoma (and adjuvant stage III indications) and specific approval/usage of dabrafenib+trametinib for BRAF V600E in glioma.

Regulatory/testing context: Clinical laboratories may offer laboratory‑developed tests under CLIA for high‑complexity testing, while the FDA maintains a list of cleared or approved companion diagnostic devices. The policy notes FDA‑approved companion diagnostics tied to several melanoma targeted therapies and that FDA approvals and NCCN recommendations (level 2A or higher) inform coverage without extensive additional evidence review. The WHO 2021 glioma classification changes are referenced as relevant to evolving molecular subtypes and targeted therapy consideration.

Evidence highlights

NCCN_recommendation_level2A or higher for listed FDA‑approved therapeutics

TMB_threshold_note>=10 mutations/megabase for pembrolizumab indication (contextual) — TMB criteria moved to MP 2.388

Medicare Determinations

NCD name/number	Effective date	Type
Next Generation Sequencing (NGS) - 90.2	2020-01-01	NCD

Revision History

11/07/2023clinical change

Minor Review: BRAF V600 testing for glioma changed from investigational to medically necessary for BRAF V600E to select dabrafenib plus trametinib.

Policy Summary

PayerCapital Bluecross

PolicySomatic Genetic Testing to Select Individuals with Melanoma or Glioma for Targeted Therapy or Immunotherapy

Policy CodePolicy MP 2.364

Change TypeClinical and administrative updates (NTRK criteriacoding changes)

Effective DateSep 1, 2025

Next Review Date

SourceLink

On This Page

Individuals with melanoma other than unresectable/metastatic or resected stage III

Insufficient evidence to support benefit

Medically Necessary - BRAF V600E testing for glioma

Testing is considered medically necessary when ALL of the following are met:

Individuals with glioma who have BRAF V600E variants

Testing to select individuals for targeted treatment with dabrafenib in combination with trametinib

Not medically necessary / Investigational - BRAF testing for glioma

Testing is considered investigational when ALL of the following are met:

Individuals with glioma for targeted treatment other than BRAF V600E-directed dabrafenib+trametinib

Insufficient evidence to support benefit

Medically Necessary - NTRK gene fusion testing

Testing is considered medically necessary when ALL of the following are met:

ONE of

Individuals with unresectable or metastatic melanoma
Testing to select individuals for treatment with FDA-approved kinase inhibitors (e.g., entrectinib, larotrectinib)
Individuals with glioma
Testing to select individuals for treatment with FDA-approved kinase inhibitors

Not medically necessary / Investigational - NTRK testing for other uses

Testing is considered investigational when ALL of the following are met:

Individuals with melanoma or glioma when testing is to select targeted treatment other than FDA-approved kinase inhibitors

Insufficient evidence to support benefit

MP 2.259 - Expanded Molecular Panel Testing
MP 2.388 - Somatic Biomarker Testing for Immune Checkpoint Inhibitor Therapy

Billing Rule

Code use and movement

Coding in this policy was updated: CPT 81210 was removed from this policy and moved to MP 2.388 (effective 05/01/2024). A new proprietary/procedure code 0473U was added effective 07/01/2024. Use the codes listed in this policy when testing is medically necessary.

0473U
81191
81192
81193
81194
81210