ModifiedAmbetter NevadaPolicy N/A

Concert Genetic Testing Oncology: Hematologic Malignancy

Defines medical necessity and coding guidance for molecular and genetic diagnostic testing for hematologic malignancies for Ambetter Nevada members, including RNA fusion panels, MRD testing, single-gene assays, and cytogenetics.

Policy Summary

PayerAmbetter Nevada

PolicyConcert Genetic Testing Oncology: Hematologic Malignancy

Policy CodePolicy N/A

Change TypeMultiple substantive additions and revisions (new RNA fusion panels, MRD criteria, CPT additions)

Effective DateN/A

Next Review DateN/A

Key ActionProviders should reference the most up-to-date sources of professional coding guidance prior to claim submission.

SourceLink

POLICY UPDATE CHANGES

Added Targeted RNA Fusion Panel Tests and Broad RNA Fusion Panel Tests and related criteria.

Replaced 'Comprehensive' with 'Broad' under Broad Molecular Profiling Panels for Hematologic Malignancies and Myeloid Malignancy Panels.

Added CPT codes 81457, 81458, 81459 to criteria for Tumor-Type Agnostic Solid Tumor Molecular Profiling Panel Tests and CPT code 0422U to MRD testing.

Panels now covered for acute lymphoblastic leukemia and criteria expanded to align with guidelines.

Retired Solid Tumor Minimal Residual Disease (MRD) criteria and replaced with two criteria sets based on LCD guidelines.

In criteria for Broad Molecular Profiling Panels For Hematologic Malignancies and Myeloid Malignancy Panels, added 'after consolidation' to a criterion point.

Hematologic Minimal Residual Disease (MRD) Testing: Added criterion that for CLL indication the member has completed treatment.

Tumor Specific NPM1 Variant Analysis: replaced requirement 'cytogenetically normal AML' with 'undergoing evaluation for acute myeloid leukemia (AML)'.

Split prior Tumor Specific IDH1/IDH2 Variant Analysis criteria into separate solid-tumor and hematologic-specific policies and replaced 'investigational' statements with language that current evidence does not support.

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majorPolicy structural changes

3CPT code additions

51+RNA fusion panel threshold

Initial workupCommon indication

ListedRelated policies

Coverage Criteria for Hematologic Molecular Testing

Broad RNA Fusion Panels for Hematologic Malignancy

Specified genetic tests are medically necessary when meeting the criteria below.

ALL of the following

Test is an RNA fusion panel utilizing RNA analysis alone with 51 or more genes
Indication: Member is undergoing diagnostic workup for adult or pediatric acute lymphoblastic leukemia (ALL)
For all other indications, RNA fusion panel tests with 51 or more genes utilizing RNA analysis alone are not supported by current evidence

Note: view rationale and background for supporting guideline references (NCCN ALL recommendations).

Broad RNA Fusion Panels for Hematologic Malignancy (>=51 genes)

Broad RNA fusion panels (>=51 genes)

ALL of the following

Panel analyzes 51 or more genes using RNA analysis alone
Indication: member is undergoing diagnostic workup for adult or pediatric acute lymphoblastic leukemia (ALL)
Current evidence does not support use of RNA-only fusion panels with >=51 genes for other indications

Definition: Broad RNA fusion panel = RNA-based fusion detection panel that analyzes 51 or more genes using RNA analysis alone.

Broad molecular profiling / Myeloid panels

Broad molecular profiling panels and myeloid malignancy panels

ONE of

Member is undergoing evaluation for acute myeloid leukemia (AML)
Member has newly diagnosed acute lymphoblastic leukemia (ALL)
Member has newly diagnosed myelodysplastic syndrome (MDS)
Suspected MDS AND other causes of cytopenia(s) have been ruled out
Suspected myeloproliferative neoplasm (MPN) AND (this is the initial genetic evaluation OR prior JAK2/CALR/MPL results were negative)

Acute Myeloid Leukemia Focused Molecular Profiling Panels

AML-focused panels

ALL of the following

Indication: Suspected or confirmed acute myeloid leukemia (AML)
Current evidence does not support AML-focused molecular profiling panels for other indications

Note: If a multigene panel is performed, appropriate panel codes should be used.

Myeloproliferative Neoplasm Panels

MPN panels

ALL of the following

Indication: Suspected myeloproliferative neoplasm (MPN)
Panel must include at minimum JAK2, CALR, and MPL
Current evidence does not support MPN panels for other indications

Note: MPN is defined in Definitions; example disease lists were removed from criteria.

Minimal Residual Disease (MRD) Testing

Hematologic MRD testing

ALL of the following

Indication: Member has diagnosis of ALL, multiple myeloma, or CLL
For CLL indication: the member has completed treatment
MRD analysis performed in bone marrow or peripheral blood
MRD may be used for baseline clone identification, serial monitoring, prognostication, and response assessment as per guideline timing (e.g., prior to induction, following consolidation, end of treatment)

Note: MRD evaluation methods may include flow cytometry, PCR, or NGS per NCCN guidance.

Tumor-specific variant and FISH analyses

Tumor-specific variant and FISH testing

ALL of the following

BCR-ABL1 kinase domain analysis: Indications include CML or Ph+ ALL with inadequate initial response to TKI, loss of response, progression to accelerated/blast phase, or relapsed/refractory disease
BCR-ABL1 FISH/qualitative/quantitative: Indicated for suspected MPN or diagnostic workup for ALL, AML, CML, lymphoblastic leukemia; quantitative tests may be used for MRD/monitoring in ALL, AML, CML
CALR variant analysis: Suspected MPN or suspected MDS
CEBPA variant analysis: Evaluation for AML
FLT3 variant analysis: Suspected/confirmed AML or diagnosis of ALL, MDS, or MPN

CLL/SLL FISH

CLL/SLL FISH Panel Analysis

ALL of the following

Indication: Initial diagnostic workup for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
Specimen: Peripheral blood or bone marrow

Note: NCCN recommends FISH testing including +12, del(11q), del(13q), del(17p) during diagnostic workup and to rule out mantle cell lymphoma with t(11;14) when indicated.

Multiple Myeloma FISH

Multiple myeloma FISH Panel Analysis

ALL of the following

Required panel contents: del(13), del(17p13), t(4;14), t(11;14), t(14;16), t(14;20), 1q21 gain/amplification, del(1p)
Indication: Initial diagnostic workup for multiple myeloma
Specimen: Bone marrow

Note: NCCN recommends these FISH analyses for prognostic purposes during initial workup.

NGS Panels and MRD

Broad molecular, fusion, and MRD testing

ALL of the following

NGS fusion and mutation testing at diagnosis: NCCN recommends comprehensive NGS testing for gene fusions and pathogenic mutations at time of diagnosis for ALL, AML, and other hematologic malignancies
MRD testing uses include baseline clone identification, serial monitoring, prognostication, and response assessment
Repeat testing is recommended for relapse, progression, or post-transplant relapse per NCCN

Note: Guideline references support timing of MRD (e.g., prior to induction, following consolidation, end of treatment) and repeat molecular testing after relapse or post-allo-HCT.

Tumor-specific testing (gene panels, FISH, PCR)

Tumor‑specific gene/assay recommendations

ALL of the following

PML-RARA rearrangement (FISH/PCR): Indicated for initial diagnostic workup for AML
BCR-ABL1 kinase domain mutation analysis: Indicated for loss of response to TKI, 1-log increase in transcripts, or progression to accelerated/blast phase in CML; relapsed/refractory Ph+ B-ALL
Gene-specific testing (examples): FLT3, NPM1, CEBPA, IDH1/2, JAK2, CALR, MPL, IGHV, TP53, etc., recommended by NCCN for diagnosis, prognosis, and treatment decision-making
Specimen modalities include blood, bone marrow, or biopsy as appropriate per test/guideline

Note: Refer to individual tumor-specific sections for detailed indication and method (FISH, PCR, sequencing).

Tumor-specific genetic testing criteria (hematologic)

Tumor-specific testing recommendations are aligned to NCCN guidance and include molecular testing (e.g., JAK2, CALR, MPL, NPM1, TP53), FISH panels for multiple myeloma and CLL/SLL, and PML-RARA rearrangement testing.

ALL of the following

MPN molecular testing: NCCN recommends molecular testing (blood or bone marrow) for suspected myeloproliferative disease; testing may be stepwise or via multigene panel including JAK2, CALR, MPL
NPM1 testing: NCCN recommends NPM1 testing during AML evaluation for prognostic or treatment implications
TP53 testing: NCCN recommends TP53 testing in AML and in mantle cell lymphoma to inform prognosis and treatment selection
Multiple myeloma FISH: NCCN recommends FISH testing during initial workup for prognostic purposes (required loci listed)

Policy updates and coverage changes

Policy-level changes to panel categories, coverage, and MRD criteria.

ALL of the following

Targeted RNA Fusion Panel Tests and Broad RNA Fusion Panel Tests and related criteria were added to the policy
Policy nomenclature: 'Comprehensive' replaced with 'Broad' under Broad Molecular Profiling Panels and Myeloid Malignancy Panels
MRD criteria update: Solid Tumor MRD criteria retired and replaced with criteria sets based on LCD guidance; CPT 0422U added to MRD references
Coverage: Panels are now covered for acute lymphoblastic leukemia and multiple tumor-specific criteria were expanded to align with NCCN guideline recommendations

Note: See coding/reference table for added CPT codes (81457-81459, 0422U) and other coding updates.

Hematologic malignancy criteria

Multiple new and revised criteria sets for hematologic molecular testing were added or updated, including MRD testing (HPV-related, evidence-based, emerging evidence), broad molecular profiling, tumor-specific variant analyses, and HLA typing for transplantation.

ALL of the following

Hematologic MRD Testing - CLL: Member must have completed treatment before MRD testing is covered for CLL indication
Broad Molecular Profiling Panels: Testing may be covered after consolidation per revised criterion II.C.1
MPN Panels: Panels must include at minimum JAK2, CALR, and MPL; lists of example MPNs removed as MPN is defined in Definitions
Tumor Specific NPM1 Variant Analysis: Coverage applies when member is undergoing evaluation for AML (replaced prior cytogenetically normal AML requirement)

Revised coverage criteria highlights

This portion documents revisions to coverage criteria for various tumor-specific and panel-based genetic tests in hematologic malignancies, including removal of example disease lists, wording clarifications, and alignment with NCCN guidance.

Coding and Test Code Reference

Example panel CPT codesCPT

81456	Broad RNA fusion panel — example billing code listed
81450	Broad molecular profiling panels — example billing code listed
81455	Broad molecular profiling panels — example billing code listed

MRD testing U-codesCPT

0364U	ClonoSEQ MRD assay — example U-code listed
0171U	MRD NGS gene panel assay — example U-code listed
0450U	M-inSight patient definition assay — example U-code listed
0451U	M-inSight patient follow-up assessment — example U-code listed

Tumor specific single-gene/cytogenetic codesCPT

81170	ABL1 kinase domain sequencing — example CPT code
81206	BCR-ABL1 FISH/cytogenetic related CPT example
81219	CALR mutation analysis — example CPT code
81218	CEBPA mutation analysis — example CPT code
81245	FLT3 variant analysis — example CPT code
81120	IDH1 variant analysis — example CPT code
81121	IDH2 variant analysis — example CPT code
81261	IGHV somatic hypermutation analysis — example CPT code
81270	JAK2 variant analysis — example CPT code
81338	MPL variant analysis — example CPT code

1–10 of 12

1/2

Multigene panel codingmixed

Use appropriate multigene panel CPT/HCPCS codes when performed (e.g., 81450, 81455 as listed in policy)

FISH panel tests (CLL/SLL and Multiple Myeloma)mixedCovered

No codes listed

MRD and broad molecular NGS panelsmixedCovered

No codes listed

Recently added CPT codesCPTCovered

0422U	CPT code added for Solid Tumor Minimal Residual Disease (MRD) testing
81457	CPT code added to Tumor-Type Agnostic Solid Tumor Molecular Profiling Panel Tests
81458	CPT code added to Tumor-Type Agnostic Solid Tumor Molecular Profiling Panel Tests
81459	CPT code added to Tumor-Type Agnostic Solid Tumor Molecular Profiling Panel Tests

Updated coding/reference tablemixed

Coding table and policy reference table updated; specific CPT/HCPCS codes present in the policy reference table (not shown in this excerpt).

coding table referencedmixed

No codes listed

inv-25: RNA fusion panel gene count threshold

ThresholdRNA fusion panels using RNA analysis alone with 51 or more genes are considered medically necessary for diagnostic workup of adult or pediatric acute lymphoblastic leukemia (ALL).

ScopeApplies to RNA-only fusion panels performed on hematologic malignancies.

Evidence limitationCurrent evidence does not support RNA fusion panels with 51+ genes (RNA-only) for indications other than diagnostic workup for ALL.

inv-26: RNA fusion panel gene count threshold — alternative mention of 51 or more genes

Provider Actions, Billing, and Authorization

Billing Rule

Coding implications and scope exclusion - liquid biopsy

This clinical policy references Current Procedural Terminology (CPT®). Codes referenced are for informational purposes only. Providers should reference the most up-to-date sources of professional coding guidance prior to the submission of claims for reimbursement. If a multigene panel is performed, appropriate panel codes should be used. These clinical criteria are not intended to address liquid biopsies (cell-free DNA); liquid biopsy assays are out of scope for the criteria in this policy and require separate clinical justification and coding considerations.

Providers should verify current CPT/ICD-10/HCPCS guidance before claim submission.
When multigene panels are performed, submit the appropriate panel codes (do not fragment into single-gene codes unless clinically and technically appropriate).
Liquid biopsies (cell-free DNA / plasma-based assays) are not addressed by these criteria and may require separate review and prior authorization.

Definitions and Test Scope

inv-39: incidental germline findings — definition of incidental germline variation

DefinitionIncidental germline variation: clinically relevant germline variants that may be uncovered during somatic mutation profiling and associated with hereditary cancer susceptibility.

Patient communicationProviders should communicate the potential for incidental germline findings with patients prior to somatic profiling.

Follow-upConfirmation of germline status may require separate germline testing and genetic counseling.

inv-40: Broad RNA fusion panel (51+ genes) — definition of RNA fusion panel (51+ genes)

DefinitionBroad RNA fusion panel (51+ genes): an RNA-based fusion detection panel that analyzes 51 or more genes using RNA analysis alone.

Intended specimen/context

Policy Summary

PayerAmbetter Nevada

PolicyConcert Genetic Testing Oncology: Hematologic Malignancy

Policy CodePolicy N/A

Change TypeMultiple substantive additions and revisions (new RNA fusion panels, MRD criteria, CPT additions)

Effective DateN/A

Next Review DateN/A

Key ActionProviders should reference the most up-to-date sources of professional coding guidance prior to claim submission.

SourceLink

On This Page

CML with progression to accelerated or blast phase OR BCR::ABL1 kinase domain mutation analysis results negative

Repeat testing when

MDS relapsed after allo-HCT
ALL with symptomatic relapse after maintenance therapy
AML relapsed or refractory after consolidation or progression on treatment

Current evidence does not support broad molecular profiling or myeloid panels in bone marrow or peripheral blood for other indications

Note: If a multigene panel is performed, appropriate panel codes should be used. These criteria do not address liquid biopsies.

IDH1/IDH2 variant analysis: Diagnosis of AML

IGHV somatic hypermutation analysis: Workup for or diagnosis of CLL, SLL, primary cutaneous B-cell lymphoma, or B-cell lymphoma

JAK2 variant analysis: Suspected MPN

MPL variant analysis: Suspected MPN or suspected MDS

NPM1 variant analysis: Evaluation for AML

TP53 variant analysis: Diagnosis of AML or ALL, or suspected MDS; referenced for CLL/SLL and mantle cell lymphoma workup

Note: See tumor-specific FISH sections for CLL/SLL and multiple myeloma panel requirements.

PML-RARA testing: NCCN includes PML-RARA among genetic markers to be tested in patients with AML; methods include qualitative FISH and PCR

CLL/SLL FISH: NCCN recommends FISH testing including +12, del(11q), del(13q), del(17p) during diagnostic workup and ruling out mantle cell lymphoma with t(11;14) when indicated

Note: These tumor-specific criteria reflect alignment with current NCCN guideline recommendations and version dates referenced in rationale/background.

Note: NCCN guideline version dates were updated across background and rationale; see references for details.

RNA fusion panel tests with 51 or more genes (51+) using RNA analysis alone.

Use caseDesignated for performance on hematologic malignancies; medically necessary for ALL diagnostic workup.

Minimum gene count51 genes or more (51+).

inv-27: Required analytes for multiple myeloma FISH panel

Required locidel(13)

Required locidel(17p13)

Required locit(4;14)

Required locit(11;14)

Required locit(14;16)

Required locit(14;20)

Required loci1q21 gain/amplification and del(1p)

inv-28: Coverage expansion — panels now covered for ALL and other coverage expansions

Coverage expansionPanels are now designated COVERED for acute lymphoblastic leukemia (ALL).

Guideline alignmentMultiple tumor-specific criteria expanded to align with NCCN guideline recommendations.

Coding updatesCoding and reference tables updated to include new CPT codes and revised mappings.

inv-29: Minimum gene list adherence — removal from reference table for noncompliant tests

Removal actionTests that fail to meet minimum gene list requirements have been removed from the policy reference table (example: Praxis Extended RAS Panel noted as removed).

EnforcementReference table adherence required to remain listed; vendors/tests must meet minimum gene content to be referenced.

ImplicationProviders should verify that a panel meets the policy's minimum gene list before relying on listed coverage guidance.

inv-30: post-consolidation timing — 'after consolidation' for certain panels

Timing noteCertain broad molecular profiling and myeloid malignancy panel criteria specify testing may be indicated 'after consolidation' (added to criterion II.C.1).

ContextThis 'after consolidation' timing applies to repeat broad molecular profiling panels for AML in the setting of relapsed/refractory disease after consolidation or progression on treatment.

Clinical alignmentChange added to align timing with NCCN guidance for post-consolidation testing and relapse evaluation.

Documentation Required

CLL/SLL FISH medical necessity

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) FISH panel analysis is considered medically necessary for members undergoing initial diagnostic workup for CLL/SLL. Ensure documentation supports that the testing is part of the initial diagnostic evaluation.

Specimen: peripheral blood or bone marrow.
Action: Include clinical documentation showing this is part of initial diagnostic workup.

Documentation Required

Multiple myeloma FISH medical necessity

Multiple myeloma FISH panel analysis of bone marrow is considered medically necessary when the panel includes specified loci and the testing is performed as part of the initial diagnostic workup.

Required loci in panel: del(13), del(17p13), t(4;14), t(11;14), t(14;16), t(14;20), 1q21 gain/amplification, and del(1p).
Specimen: bone marrow.
Action: Document that testing is for initial diagnostic workup of multiple myeloma.

Prior Authorization

Prior authorization and criteria updates

Prior authorization is likely required for many molecular and cytogenetic panels referenced in this policy. Providers should verify current prior authorization requirements and submit supporting clinical documentation that meets the applicable criteria to avoid denials or delays.

Confirm payer-specific prior authorization requirements before ordering/testing.
Include clinical notes specifying indication (e.g., initial diagnostic workup, relapse, post-transplant evaluation) and prior test results when required (e.g., negative JAK2/CALR/MPL for certain MPN panels).
Revised criteria may expand coverage for certain panels (for example, panels designated COVERED for acute lymphoblastic leukemia); verify the applicable criteria set at time of submission.

Note

Operational flags

Operational flags — areas where provider action is commonly required to ensure appropriate processing and reimbursement.

prior_auth: Verify and obtain prior authorization when required.
denial_risk: Tests performed without documentation meeting the criteria risk denial.
documentation: Ensure clinical indication and prior testing (when relevant) are included in the record.
billing_rule: Use appropriate panel CPT codes for multigene panels; inclusion of codes in the policy is informational only.
step_therapy: Follow any payer-specified testing pathways or sequencing requirements.

Performed on hematologic malignancies for diagnostic workup; recommended by NCCN for ALL comprehensive molecular characterization.

Coverage limitationMedically necessary for diagnostic workup of adult or pediatric ALL; not supported for all other indications per current evidence.

inv-41: Broad RNA fusion panel — RNA fusion panel tests with 51 or more genes utilizing RNA analysis alone

Test descriptionRNA fusion panel tests with 51 or more genes that utilize RNA analysis alone (RNA-only fusion detection assays).

Coverage criteriaConsidered medically necessary when performed on hematologic malignancies for diagnostic workup of ALL.

Evidence statementPolicy states current evidence does not support RNA-only 51+ gene fusion panels for indications beyond ALL.

inv-42: Panels performed on bone marrow or peripheral blood — definition for broad molecular profiling panels in hematologic/myeloid malignancies

DefinitionBroad molecular profiling panels performed on bone marrow or peripheral blood for hematologic/myeloid malignancies, including NGS multigene panels for prognostication and therapy guidance.

Specimen typesBone marrow or peripheral blood specimens as appropriate per disease indication.

IndicationsIncludes initial evaluation of suspected MDS, newly diagnosed ALL, AML evaluation, suspected MPNs, and repeat testing for relapse or post-transplant relapse.

inv-43: MRD — definition of Minimal Residual Disease testing

DefinitionMinimal Residual Disease (MRD) testing: assays (flow cytometry, PCR, or NGS) used for baseline clone identification, serial monitoring, prognostication, and response assessment at defined time points (e.g., prior to induction, following consolidation, end of treatment).

NCCN recommendationsNCCN recommends MRD testing in ALL, multiple myeloma, and CLL/SLL at specified time points including end of treatment for CLL/SLL.

Specimen and methodsMRD analysis can be performed on bone marrow or peripheral blood using flow cytometry, PCR, or NGS assays.

inv-44: NGS panel — definition for NGS multigene panels and their uses

DefinitionNGS panel: next-generation sequencing multigene panels used for molecular profiling and prognostication, including detection of gene fusions and pathogenic mutations to guide prognosis and therapy.

UsesUsed for diagnostic evaluation, prognostication, therapy selection, and monitoring in hematologic malignancies per NCCN guidance.

Panel compositionMay include genes with prognostic/therapeutic implications such as FLT3, NPM1, CEBPA, IDH1/2, JAK2, CALR, MPL, TP53, and others.

inv-45: MPN — Myeloproliferative Neoplasm definition

DefinitionMyeloproliferative Neoplasm (MPN): a rare blood disease in which the bone marrow makes too many red blood cells, white blood cells, or platelets; includes subcategories such as CML, PV, PMF, ET, chronic neutrophilic leukemia, chronic eosinophilic leukemia, and MPN-U.

Panel requirementMPN panels must include, at minimum, testing of JAK2, CALR, and MPL.

Documentation changeExample lists of MPNs were removed from criteria sets since MPN is defined in the Definitions section.

inv-46: MPN — MPN definition referenced — example lists removed from criteria

Definition noteMPN is defined in the Definitions section; example lists of MPNs were removed from criteria to avoid redundancy.

Policy effectCriteria sets referencing MPN now rely on the Definitions section rather than re-listing examples.

Related editsMultiple criteria updated to remove example disease lists where MPN is referenced.

inv-47: MPN definition referenced — note that MPN is defined in Definitions and example lists were removed from criteria

Standard definitionMPN (myeloproliferative neoplasm) is defined in the Definitions section and is the referenced term across multiple criteria sets.

Cross-referenceCriteria for CALR, JAK2, and MPL variant analyses were updated to remove example MPN lists and reference Definitions.

Operational noteProviders should consult the Definitions section for the full, authoritative MPN definition when applying criteria.

inv-48: MPN (myeloproliferative neoplasm) — MPN definition used by multiple criteria sets

DefinitionMPN (myeloproliferative neoplasm): a defined term in the policy's Definitions section listing subcategories (e.g., CML, PV, PMF, ET, chronic neutrophilic/eosinophilic leukemias, MPN-U).

Use in criteriaThis standardized MPN definition is applied across multiple criteria sets to ensure consistency.

ImplicationExample disease lists were removed from individual criteria to reduce duplication and rely on this Definitions entry.