ModifiedUnitedHealthcarePolicy CS372NE.E

Molecular Oncology Testing for Hematologic Cancer Diagnosis, Prognosis, and Treatment Decisions (for Nebraska Only)

Policy governing coverage of molecular and genomic testing (multigene panels, comprehensive genomic profiling, MRD/clonality testing) for diagnosis, prognosis, and treatment decisions in hematologic malignancies for Nebraska members and providers.

Policy Summary

PayerUnitedHealthcare

PolicyMolecular Oncology Testing for Hematologic Cancer Diagnosis, Prognosis, and Treatment Decisions (for Nebraska Only)

Policy CodePolicy CS372NE.E

Change TypeCoverage criteria revised and expandedadded and clarified indications

Effective DateFeb 1, 2026

Next Review DateN/A

Key ActionOrder multigene panels (≤50 genes), CGP, or clonoSEQ only when requested by a hematologist or oncologist and document medical necessity in the patient record.

SourceLink

POLICY UPDATE CHANGES

Added language to clarify the use of multigene panels (50 genes or fewer) at initial diagnosis and/or recurrence or relapse is proven and medically necessary when ordered by a hematologist or oncologist for individuals with the listed conditions.

Replaced wording requiring 'strongly suspected' MDS/MPN with 'suspected' (as evidenced by order from a hematologist/oncologist) for multigene panel coverage.

Added chronic lymphocytic leukemia (CLL) as a covered indication for clonoSEQ® clonality assessment at initial diagnosis and MRD assessment with clonoSEQ.

Expanded proven and medically necessary indications for Comprehensive Genomic Profiling (CGP) to include acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, and myeloproliferative neoplasm.

Clarified that molecular tests other than clonoSEQ are unproven and not medically necessary for initial clonality assessment or for assessment of measurable residual disease (MRD).

Added medical records documentation language describing required documentation to support medical necessity and noting that documentation may be required for review and does not guarantee coverage.

Nebraskastate applicability

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.

≤50panel gene threshold

clonoSEQnamed MRD assay

02/01/2026policy effective

OGM, WTSnot medically necessary examples

Coverage Criteria for Molecular & Genomic Testing

Multigene panels (≤50 genes)

Covered when ordered by a hematologist or oncologist for initial diagnosis and/or recurrence/relapse.

Hematologic indications for multigene panels: Acute lymphoblastic leukemia OR Acute myeloid leukemia OR Multiple myeloma OR Myelodysplastic syndrome or myeloproliferative neoplasm is suspected (as evidenced by order from hematologist/oncologist)panel <= 50 genes

Multigene panels (50 genes or fewer) are proven and medically necessary when ordered by a hematologist or oncologist

Comprehensive Genomic Profiling (CGP)

Comprehensive Genomic Profiling (CGP) is proven and medically necessary for the following indications.

Indications for CGP: Acute lymphoblastic leukemia OR Acute myeloid leukemia OR Myelodysplastic syndrome OR Myeloproliferative neoplasmCGP (e.g., FoundationOne Heme, Neo Comprehensive - Heme, NEO AML Express)

CGP considered proven and medically necessary for these hematologic malignancies

Clonality assessment and MRD testing

Clonality and MRD assessment with clonoSEQ are proven and medically necessary when ordered by a hematologist or oncologist for the following indications.

ClonoSEQ indications: Acute lymphoblastic leukemia OR Multiple myeloma OR Chronic lymphocytic leukemiaassay = clonoSEQ

Other molecular tests for clonality or MRD are unproven and not medically necessary

Evidence summaries and contexts

Findings across studies indicating when MRD testing is prognostic or may inform therapy decisions:

General prognostic value: MRD negativity by sensitive assays (NGS/HTS) is associated with improved progression-free survival (PFS), disease-free survival (DFS), and overall survival (OS) across multiple hematologic malignancies (ALL, CLL, AML, MM).varies by study (10^-4 to 10^-6)

Supported by cohort studies, pooled analyses, and FDA review of clonoSEQ

Examples of clinical contexts with demonstrated prognostic MRD value: CLL: undetectable MRD associated with longer PFS (CLL14); ALL: NGS MRD negativity after induction correlated with very low 5-year relapse; MM: MASTER and pooled daratumumab trials used NGS MRD thresholds (eg, <10^-5) linked to improved PFS; AML: NGS and flow cytometry combined add prognostic value for relapse and survival.study-specific

See cited studies for details

Limitations and recommendations:

Use of Multigene Panels (50 Genes or Fewer) at Initial Diagnosis and/or Recurrence or Relapse

Key coverage determinations and notable revision items (partial):

Multigene panels (<=50 genes): Multigene panels (50 genes or fewer) at initial diagnosis and/or recurrence or relapse are proven and medically necessary when ordered by a hematologist or oncologist for individuals with the listed hematologic conditions.genes <= 50

Policy clarified 02/01/2026

Clonality Assessment and MRD Assessment With clonoSEQ

clonoSEQ use: clonoSEQ is indicated for clonality assessment at initial diagnosis and for MRD assessment when the individual has chronic lymphocytic leukemia or other specified indications listed in the policy.assay = clonoSEQ

Molecular tests other than clonoSEQ are unproven and not medically necessary for initial clonality assessment or MRD assessment

Comprehensive Genomic Profiling (CGP) — single top-level node

Comprehensive Genomic Profiling (single top-level determination):

CGP proven indications: Use of Comprehensive Genomic Profiling (examples: FoundationOne Heme, Neo Comprehensive - Heme Cancers, NEO AML Express) is proven and medically necessary for individuals with acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasm.test in examples

Coverage expanded to include ALL and additional example tests

Covered Indications for Genetic and Molecular Testing

Policy affirms certain genetic and molecular tests are proven and medically necessary when ordered by a hematologist or oncologist for specified hematologic malignancies.

Multigene panels (≤50 genes): Use of multigene panels (50 genes or fewer) at initial diagnosis and/or recurrence or relapse is proven and medically necessary when ordered by a hematologist or oncologist for individuals with the listed conditions.panel_size <= 50

Ordering clinician specialty must be documented

Comprehensive Genomic Profiling: CGP (eg, FoundationOne Heme, Neo Comprehensive - Heme Cancers, NEO AML Express) is proven and medically necessary for individuals with ALL, AML, MDS, or MPN.

Expanded indications per revision

Clonality and MRD assessment: Clonality assessment and MRD assessment with clonoSEQ are proven and medically necessary when criteria are met; clonoSEQ indication expanded to include chronic lymphocytic leukemia.

The policy states that molecular tests other than clonoSEQ® for initial clonality assessment or for assessment of measurable residual disease (MRD) are considered unproven and not medically necessary. The revision clarifies that clonoSEQ® is the named assay for clonality and MRD assessment when determining medical necessity and that other molecular assays are not supported for these purposes (see policy Coverage Rationale and Revision summary).

Professional guideline groups note that although MRD status is prognostic, there is insufficient evidence to change maintenance therapy or alter type/length of therapy based on MRD status outside clinical trials. ASCO/CCR guidance advises that MRD-negative status should not be used to guide treatment decisions outside trial contexts; expert consensus for CLL similarly states routine MRD testing to guide therapy is not currently recommended and remains a subject for clinical studies.

Consistent with the Coverage Rationale and recent revision, the policy reiterates that the use of molecular tests other than clonoSEQ® for initial clonality assessment or MRD assessment is unproven and not medically necessary, and such uses are not covered.

The policy further clarifies in the revision history that molecular assays other than clonoSEQ® remain characterized as unproven and not medically necessary for initial clonality assessment and for MRD assessment, and this position was explicitly restated when the policy language was updated.

Examples of molecular tests and platforms identified in the policy as not supported for MRD or clonality assessment include optical genome mapping and whole transcriptome sequencing; the policy states these and other broad molecular panels for hematologic cancer are unproven and not medically necessary.

Guideline context emphasizes that MRD assessment has prognostic value but routine MRD testing to guide treatment decisions is not currently recommended for certain diseases (for example, CLL and for altering maintenance therapy in multiple myeloma) outside the context of clinical trials. Expert consensus and ASCO/CCR guidance recommend further study and standardized approaches before MRD can routinely direct therapy changes.

In summary, the policy's coverage stance is clear: molecular tests other than clonoSEQ® for initial clonality assessment or MRD assessment are unproven and not medically necessary and therefore are not covered for those indications.

Policy clarification in the revision history reiterates that non-clonoSEQ molecular assays used for clonality or MRD assessment are unproven and not medically necessary; this reinforces the specific coverage distinction between clonoSEQ® (covered when criteria met) and other molecular tests (not covered for these uses).

Covered Indications by Disease

Acute lymphoblastic leukemia (ALL) — coverage details

Coverage details specific to acute lymphoblastic leukemia (ALL):

CGP and MRD in ALL: CGP is indicated as proven and medically necessary for individuals with ALL; clonoSEQ NGS MRD assessment has demonstrated prognostic value (sensitivity examples to 10^-6) and is considered medically necessary for clonality and MRD assessment when ordered by a hematologist/oncologist.NGS sensitivity up to 10^-6

NGS MRD negativity after induction in cited study associated with no relapses at 5 years

Acute myeloid leukemia (AML) — coverage details

Coverage details specific to acute myeloid leukemia (AML):

Multigene panels and CGP in AML: Multigene panels (≤50 genes) and CGP are proven and medically necessary for individuals with AML when ordered by a hematologist or oncologist; targeted NGS at diagnosis facilitates mutation-based MRD tracking.

Applicable Codes & Coding Notes

Applicable molecular/genomic procedure codesmixed

0017M	Oncology (diffuse large B-cell lymphoma [DLBCL]), mRNA, gene expression profiling by fluorescent probe hybridization of 20 genes, formalin-fixed paraffin-embedded tissue, algorithm reported as cell of origin.
0050U	Targeted genomic sequence analysis panel, acute myelogenous leukemia, DNA analysis, 194 genes, interrogation for sequence variants, copy number variants or rearrangements.
0120U	Oncology (B-cell lymphoma classification), mRNA, gene expression profiling by fluorescent probe hybridization of 58 genes (45 content and 13 housekeeping genes), formalin-fixed paraffin- embedded tissue, algorithm reported as likelihood for primary mediastinal B-cell lymphoma (PMBCL) and diffuse large B-cell lymphoma (DLBCL) with cell of origin subtyping in the latter
0171U	Targeted genomic sequence analysis panel, acute myeloid leukemia, myelodysplastic syndrome, and myeloproliferative neoplasms, DNA analysis, 23 genes, interrogation for sequence variants, rearrangements and minimal residual disease, reported as presence/absence.
0298U	Oncology (pan tumor), whole transcriptome sequencing of paired malignant and normal RNA specimens, fresh or formalin-fixed paraffin-embedded (FFPE) tissue, blood or bone marrow, comparative sequence analyses and expression level and chimeric transcript identification.
0299U	Oncology (pan tumor), whole genome optical genome mapping of paired malignant and normal DNA specimens, fresh frozen tissue, blood, or bone marrow, comparative structural variant identification.
0300U	Oncology (pan tumor), whole genome sequencing and optical genome mapping of paired malignant and normal DNA specimens, fresh tissue, blood, or bone marrow, comparative sequence analyses and variant identification.
0331U	Oncology (hematolymphoid neoplasia), optical genome mapping for copy number alterations and gene rearrangements utilizing DNA from blood or bone marrow, report of clinically significant alterations.
0364U	Oncology (hematolymphoid neoplasm), genomic sequence analysis using multiplex (PCR) and next-generation sequencing with algorithm, quantification of dominant clonal sequence(s), reported as presence or absence of minimal residual disease (MRD) with quantitation of disease burden, when appropriate.
0413U	Oncology (hematolymphoid neoplasm), optical genome mapping for copy number alterations, aneuploidy, and balanced/complex structural rearrangements, DNA from blood or bone marrow, report of clinically significant alterations.

1–10 of 20

1/2

No CPT/HCPCS/ICD codes provided in these chunksmixed

No codes listed

Panel gene count threshold (≤ 50 genes)

Panel gene count thresholdMultigene panels of 50 genes or fewer are considered proven and medically necessary when ordered by a hematologist or oncologist for initial diagnosis and/or recurrence or relapse.

Policy effective dateRevision adding 50-gene threshold effective 02/01/2026.

Ordering clinicianMust be ordered by a hematologist or oncologist (order must evidence suspicion or diagnosis of the relevant hematologic condition).

MRD assay sensitivity thresholds (examples)

Example MRD sensitivity thresholdsAssay sensitivity examples cited include 10^-4, 10^-5, and 10^-6.

Flow cytometry sensitivity

Provider Obligations, Ordering & Documentation

Billing Rule

Applicable Codes & Billing

Applicable coding and billing rules (including CPT/HCPCS/ICD-10 codes) referenced in this policy may be subject to additional coverage rules, prior authorization, or documentation requirements. Verify applicable benefit plan, state, and federal requirements prior to billing.

Codes referenced in policy may be subject to coverage rules and should be confirmed against the member's plan

Prior Authorization

Prior authorization is not specifically required by this policy text, but coverage decisions remain subject to the member's federal, state, or contractual benefit requirements which may impose prior authorization. Always check the member's benefit plan and any applicable payer-specific prior authorization resources before ordering tests.

Not Covered / Unproven Services

This policy section explicitly states that molecular tests other than clonoSEQ® (including broad molecular panels outside proven uses) are considered unproven and not medically necessary for initial clonality or MRD assessment and may be denied when submitted for those purposes.

Within the cited chunks there are no explicit test exclusions listed beyond the general statements that molecular tests other than clonoSEQ® are unproven and not medically necessary for clonality/MRD assessment.

The policy reiterates that molecular tests other than clonoSEQ® for initial clonality assessment or MRD assessment are unproven and not medically necessary, and thus are not covered when used for those purposes.

Restating the policy position, the revision history clarifies that molecular tests other than clonoSEQ® for initial clonality assessment or MRD assessment are not covered because they are unproven and not medically necessary.

Definitions and Key Terms

Comprehensive Genomic Profiling (CGP) definition

DefinitionComprehensive Genomic Profiling (CGP): A type of Next Generation Sequencing (NGS) test able to detect all classes of genomic alterations, including cancer biomarkers, from a single sample.

Example testsPolicy examples include FoundationOne® Heme, Neo Comprehensive™ - Heme Cancers, and NEO AML Express™.

Covered indicationsCGP is proven and medically necessary for individuals with ALL, AML, MDS, or myeloproliferative neoplasm when ordered by a hematologist or oncologist.

Measurable Residual Disease (MRD) definition

DefinitionMeasurable Residual Disease (MRD): Very small number of cancer cells detectable during or after treatment using sensitive methods (PCR, flow cytometry, NGS); presence below morphologic detection associated with relapse risk.

Background and Clinical Context

Background: Hematologic malignancies arise from blood-forming tissues and often require molecular profiling to inform diagnosis, prognosis, and therapy selection. The policy recognizes that molecular profiling methods range from targeted multigene panels and CGP to clonality/NGS MRD assays such as clonoSEQ®, and that clonoSEQ® has evidence supporting improved standardization and sensitivity compared with other techniques (per NICE briefing), while randomized outcome data remain limited.

Policy Summary

PayerUnitedHealthcare

PolicyMolecular Oncology Testing for Hematologic Cancer Diagnosis, Prognosis, and Treatment Decisions (for Nebraska Only)

Policy CodePolicy CS372NE.E

Change TypeCoverage criteria revised and expandedadded and clarified indications

Effective DateFeb 1, 2026

Next Review DateN/A

Key ActionOrder multigene panels (≤50 genes), CGP, or clonoSEQ only when requested by a hematologist or oncologist and document medical necessity in the patient record.

SourceLink

On This Page

Although MRD negativity is prognostic, evidence is limited regarding whether MRD-guided changes in therapy improve long-term outcomes; guidelines recommend MRD assessment for prognostication and clinical trials and advise caution in routine treatment changes outside trials.

Guideline cautions and trial-context evidence summarized

Other molecular MRD tests are unproven and not medically necessary

panel <= 50 genes; targeted NGS examples (eg, 54-gene AML panels)

NGS-based MRD provides prognostic information though sensitivity may be ~10^-4 to 10^-5

Multiple myeloma — coverage details

Coverage details specific to multiple myeloma (MM):

CGP and MRD in MM: Multigene panels (≤50 genes) and CGP are proven and medically necessary when ordered by a hematologist or oncologist for individuals with MM; MRD assessment by sensitive NGS assays (eg, thresholds cited at 10^-5) is prognostic and was used to guide therapy in trials (eg, MASTER).study-specific (eg, MRD <10^-5)

MRD-guided therapy has been evaluated in trials but generalizability varies by risk group

Myelodysplastic syndrome (MDS) — coverage details

Coverage details specific to myelodysplastic syndrome (MDS):

Multigene panels and CGP in MDS: Multigene panels (≤50 genes) at initial diagnosis and CGP are proven and medically necessary for individuals with myelodysplastic syndrome when ordered by a hematologist or oncologist.panel <= 50 genes

Policy language revised to 'suspected' for MDS/MPN criteria

Myeloproliferative neoplasm (MPN) — coverage details

Coverage details specific to myeloproliferative neoplasm (MPN):

Multigene panels and CGP in MPN: Multigene panels (≤50 genes) at initial diagnosis and CGP are proven and medically necessary for individuals with myeloproliferative neoplasm when ordered by a hematologist or oncologist.panel <= 50 genes

Policy wording clarified regarding 'suspected' MDS/MPN

Chronic lymphocytic leukemia (CLL) — added for clonoSEQ clonality/MRD

Coverage details specific to chronic lymphocytic leukemia (CLL):

clonoSEQ in CLL: clonoSEQ is indicated for clonality assessment at initial diagnosis and for MRD assessment in individuals with chronic lymphocytic leukemia when ordered by a hematologist or oncologist; other molecular MRD tests are unproven and not medically necessary.assay = clonoSEQ

FDA clearance supports clonoSEQ clinical validity in CLL

MRD assessment for prognostication and monitoring in ALL, MM, CLL, and AML

MRD assessment for prognostication and monitoring in ALL, MM, CLL, and AML:

Prognostic MRD assessment: NGS/HTS MRD assays provide prognostic information across ALL, MM, CLL, and AML and are considered clinically informative for risk stratification and monitoring when used in appropriate clinical contexts.sensitivity varies (eg, 10^-4 to 10^-6)

Assay-specific sensitivities and clinical context determine interpretation

CGP for individuals with ALL, AML, MDS, or MPN (examples listed)

CGP examples and indication summary for hematologic malignancies:

CGP examples for blood cancers: Examples of CGP tests include FoundationOne Heme, Neo Comprehensive - Heme Cancers, and NEO AML Express; CGP is proven and medically necessary for individuals with ALL, AML, MDS, or MPN.test in examples

Expanded coverage language replaces prior relapsed/recurrent AML-only wording

Multigene panels (≤50 genes) at initial diagnosis and/or recurrence or relapse — covered indications

Multigene panels (≤50 genes) at initial diagnosis and/or recurrence or relapse — covered indications:

Covered indications: Acute lymphoblastic leukemia OR Acute myeloid leukemia OR Multiple myeloma OR Myelodysplastic syndrome or myeloproliferative neoplasm is suspected (as evidenced by order from hematologist/oncologist)panel <= 50 genes

Must be ordered by a hematologist or oncologist

Clonality assessment and MRD assessment with clonoSEQ, including for CLL

Clonality assessment and MRD assessment with clonoSEQ, including for CLL:

clonoSEQ covered uses: Clonality assessment at initial diagnosis OR MRD assessment when ordered by a hematologist or oncologist for Acute lymphoblastic leukemia OR Multiple myeloma OR Chronic lymphocytic leukemiaassay = clonoSEQ

Other molecular tests for clonality/MRD are unproven and not medically necessary

CGP proven/medically necessary for ALL, AML, MDS, MPN

CGP proven/medically necessary coverage statement for listed hematologic malignancies:

CGP proven indications: Comprehensive Genomic Profiling (CGP) is proven and medically necessary for individuals with acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasm.

Examples: FoundationOne Heme, Neo Comprehensive - Heme Cancers, NEO AML Express

CLL added as indication for clonoSEQ

CLL added as an indication for clonoSEQ:

CLL added: Chronic lymphocytic leukemia is included as an indication for clonoSEQ clonality assessment at initial diagnosis and for MRD assessment.assay = clonoSEQ

Added in policy revision

Multicolor flow cytometry (MFC) analytic sensitivity approximately 0.01% (1 × 10^-4).

ASO‑PCR sensitivityAllele‑specific oligonucleotide PCR (ASO‑PCR) analytic sensitivity approximately 0.001% (10^-5 to 10^-6).

Recommended MRD assay sensitivity

Recommended minimum MRD sensitivityGuidelines recommend validated MRD assessment technology with sensitivity of 10^-4 or better (NCCN).

Greater assay sensitivity possibleSome NGS-based assays (e.g., clonoSEQ) can detect MRD down to 10^-6.

Guideline usageIf MRD is negative by flow cytometry, an FDA‑approved NGS assay is recommended for consideration to confirm negativity.

Multigene panel size restated (≤ 50 genes)

Restated multigene panel sizePolicy specifies multigene panels of 50 genes or fewer for covered use at initial diagnosis and/or recurrence or relapse.

Covered indicationsApplies when ordered for ALL, AML, multiple myeloma, or when MDS/MPN is suspected as evidenced by order from a hematologist/oncologist.

Relation to CGPCGP is a separate category; multigene panels ≤50 genes are distinct from broader CGP panels referenced elsewhere in the policy.

No explicit prior authorization requirement stated in policy chunks; verify member-specific requirements prior to testing

Note

Ordering Restrictions for Multigene Panels and CGP

Multigene panels (50 genes or fewer) and comprehensive genomic profiling (CGP) for the covered indications must be ordered by a hematologist or oncologist. Orders should document the suspected or confirmed diagnosis that supports medical necessity (for example, AML, ALL, multiple myeloma, MDS, or myeloproliferative neoplasm).

Multigene panels (≤50 genes) — must be ordered by a hematologist or oncologist
Comprehensive Genomic Profiling (CGP) — recommended to be ordered by a hematologist or oncologist for covered indications

Prior Authorization

Specialist Ordering Requirement

Specialist ordering requirement: tests considered proven and medically necessary (including multigene panels ≤50 genes and clonoSEQ® for clonality/MRD) must be ordered by a hematologist or oncologist. Ensure the ordering provider's specialty and the clinical indication are clearly documented in the medical record.

Ordering provider must be hematologist or oncologist for proven/medically necessary tests
Documentation should evidence the suspicion or diagnosis (e.g., MDS suspected as evidenced by order from hematologist/oncologist)

Documentation Required

Documentation Requirements

Medical records must fully support medical necessity. Required documentation may include relevant medical history, physical examination findings, diagnostic test results, pathology/cytogenetic reports, and the ordering clinician’s rationale. Documentation must be legible and available upon request. Failure to provide adequate documentation may result in denial of coverage.

Document relevant history, exam, and pertinent diagnostic test or procedure results
Maintain legible records and make available upon request
Lack of documentation may result in denial

Documentation Required

Specimen & Testing Documentation

Specimen and testing documentation should demonstrate adequate sample quality and any ancillary testing performed (e.g., flow cytometry, cytogenetics, FISH, PCR) as required by guidelines (CAP/ASH). Ensure the laboratory report includes assay type, sensitivity (e.g., NGS MRD sensitivity), and whether unique clonotype sequences were identified for clonoSEQ® when applicable.

Ensure adequate sample and ancillary testing documented (flow cytometry, karyotype, FISH, molecular tests)
Report assay type and sensitivity; document clonotype availability for clonoSEQ® tracking

Denial Risk

Denial risk exists for services that lack supporting documentation, are ordered by non-specialists when specialist ordering is required, or are for molecular tests other than clonoSEQ® for clonality or MRD assessment. Services outside the stated coverage criteria (including unproven tests such as optical genome mapping or whole transcriptome sequencing) may be denied.

Denial risk for non-clonoSEQ® molecular MRD tests and other unproven molecular panels
Denial risk if documentation does not support medical necessity or ordering specialty requirement not met

Note

Use of Utilization Management Tools

UnitedHealthcare may use third-party utilization management tools (for example, InterQual®) to assist in administration of benefits. Use these tools and payer resources as part of pre-authorization and coverage determination workflows when applicable.

InterQual® and similar third-party tools may be used to assist coverage determinations

MRD measurement is most often used for blood cancers and can inform prognosis and treatment planning (timing and methods vary by disease/guideline).

Common specimen sourcesMRD detection typically uses blood or bone marrow specimens depending on disease and assay used.

Next Generation Sequencing (NGS) definition

DefinitionNext Generation Sequencing (NGS): Sequencing techniques that rapidly analyze multiple DNA sections simultaneously, enabling high-throughput detection of genomic alterations and sensitive MRD assays.

Use in MRD and CGPNGS underlies both comprehensive genomic profiling (CGP) and high-sensitivity MRD assays (e.g., HTS of IG/TR genes or commercial assays such as clonoSEQ).

Sensitivity advantageNGS-based MRD assays can achieve sensitivities greater than flow cytometry (down to 10^-6 in some assays).

MRD negativity thresholds (10^-4, 10^-5, 10^-6)

MRD negativity thresholdsMRD negativity is reported at assay‑specific sensitivity thresholds such as 10^-4, 10^-5, or 10^-6.

Assay examplesFlow cytometry ~10^-4; ASO‑PCR ~10^-5 to 10^-6; some NGS assays report to 10^-6.

Clinical implicationReported MRD negativity depends on assay sensitivity; absence of detectable MRD does not fully rule out residual disease at lower levels than assay sensitivity.

Analytic methods (MFC, ASO-PCR, high-throughput sequencing)

Analytic methods listCommon analytic methods include multicolor flow cytometry (MFC), allele‑specific oligonucleotide PCR (ASO‑PCR), and high‑throughput sequencing/NGS of immunoglobulin/T‑cell receptor genes or targeted mutation panels.

Flow cytometryMFC typically has analytic sensitivity around 0.01% (10^-4) and is widely used for MRD immunophenotype detection.

ASO‑PCR and HTSASO‑PCR offers sensitivity ~10^-5 to 10^-6 but requires patient‑specific probes; HTS/NGS methods provide high sensitivity and broader applicability.

MRD definition and common assay methods

MRD definition and scopeMRD denotes residual malignant cells below morphologic detection; MRD assays include flow cytometry, PCR‑based methods, and NGS‑based assays with varying sensitivities (approximately 10^-4 to 10^-6).

Clinical utilityMRD status is prognostic across hematologic malignancies (ALL, AML, CLL, MM) but guideline recommendations caution routine MRD‑guided treatment changes outside trials.

Assay selectionAssay choice depends on disease, required sensitivity, and whether clonality (IGH/TR) or mutation‑based tracking is performed.

CGP definition (broad NGS-based panels)

CGP as broad NGS panelsComprehensive genomic profiling (CGP) refers to broad NGS‑based panels designed to detect mutations, fusions, and other alterations relevant to hematologic malignancies.

ExamplesPolicy lists example CGP tests: FoundationOne® Heme, Neo Comprehensive™ - Heme Cancers, NEO AML Express™.

Clinical purposeCGP is used for detection of classes of genomic alterations to inform diagnosis, prognosis, and targeted therapy selection in hematologic cancers.

Named assay clonoSEQ® (restricted for molecular clonality/MRD assessments)

Named assay restrictionclonoSEQ® is the specified molecular clonality/MRD assay referenced in the policy; molecular tests other than clonoSEQ are described as unproven and not medically necessary for initial clonality assessment or MRD assessment.

Indications for clonoSEQ®clonoSEQ® is indicated for clonality assessment at initial diagnosis and for MRD assessment in ALL, multiple myeloma, and chronic lymphocytic leukemia when ordered by a hematologist or oncologist.

Policy instructionUse of other molecular MRD/clonality tests may be denied as unproven and not medically necessary per the policy.

Examples of CGP tests considered proven/medically necessary

Example CGP tests considered proven/necessaryPolicy examples of CGP tests considered proven and medically necessary include FoundationOne® Heme, Neo Comprehensive™ - Heme Cancers, and NEO AML Express™.

IndicationsThese CGP tests are indicated for individuals with ALL, AML, MDS, or myeloproliferative neoplasm when ordered by a hematologist or oncologist.

Policy change notePolicy revision expanded CGP proven indications and added NEO AML Express™ to the example list (02/01/2026).