UnitedHealthcare Molecular Oncology Coverage Update

Coverage Criteria

Medically necessary indications

Covered when ALL of the following are met for specified tests/indications

Comprehensive Genomic Profiling (CGP) is medically necessary for individuals with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or myeloproliferative neoplasm (MPN).

Refer to InterQual CP: Molecular Diagnostics for clinical coverage criteria.

Multigene panels (<=50 genes) at initial diagnosis/recurrence: Multigene panels (50 genes or fewer) at initial diagnosis and/or recurrence or relapse are medically necessary when ordered by a hematologist or oncologist for individuals with acute lymphoblastic leukemia, multiple myeloma, or chronic lymphocytic leukemia.<=50 genes

Ordered by a hematologist or oncologist per policy.

Clonality assessment (clonoSEQ): Clonality assessment with clonoSEQ Clonality ID is proven and medically necessary in certain circumstances when criteria per InterQual CP: Molecular Diagnostics are met.

See InterQual CP: Molecular Diagnostics for specific indications and criteria.

Unproven and not medically necessary

Not covered / unproven

Unproven molecular panels: All other molecular test panels for hematologic cancer not specified as proven (including but not limited to optical genome mapping and whole transcriptome sequencing) are considered unproven and not medically necessary.

Insufficient evidence of efficacy per policy.

Contexts where MRD testing has supportive evidence

Evidence indicates MRD testing may be clinically useful when ALL of the following contextual conditions are met:

Evidence-supported contexts for MRD: MRD testing using high-sensitivity methods (e.g., NGS/HTS, ASO-PCR, or validated multiparameter flow cytometry) to inform prognosis and to guide time-limited or response-adapted therapy in clinical trial or specialized-care settings for CLL, ALL, MM, and AML.

Supported by randomized and nonrandomized trials and meta-analyses (e.g., FLAIR, MASTER, pooled MM trials, CLL meta-analysis) showing associations between MRD-negativity and improved PFS/OS or used to direct therapy duration in trial protocols.

Evidence limitations

Considerations that may limit routine coverage:

Evidence limitations and cautions: Heterogeneity of assays, specimen types, timing of assessment, and analytic sensitivity across studies; lack of standardized thresholds and limited randomized data demonstrating improved clinical outcomes from MRD-guided management in routine practice for some indications (e.g., CLL); guideline statements currently do not recommend routine MRD testing in CLL outside clinical trials.

These limitations may restrict coverage to clinical trials or defined specialized-care scenarios.

MRD general criteria

Guideline-based uses and considerations for MRD testing in hematologic malignancies

General MRD criteria: Use validated MRD assessment technology with sensitivity of 10^-4 or better; consider FDA‑cleared NGS assays to confirm flow cytometry negativity; obtain baseline clonotype or molecular profiling at diagnosis when needed to enable future NGS MRD tracking.sensitivity >= 10^-4

Multiple guideline bodies (NCCN, EHA/ESMO, ASCO/CCR, CAP/ASH) provide recommendations on assay sensitivity, timing, and specimen choice; routine therapy changes based solely on MRD often not recommended outside trials.

Disease-specific guidance

Selected disease-specific recommendations from NCCN/ESMO/ASCO

ALL (acute lymphoblastic leukemia): NCCN: perform molecular characterization (FISH, RT‑PCR, NGS) and use validated MRD assays (sensitivity 10^-4 or better) at defined time points (end of induction, end of consolidation, and regimen-specific intervals); consider FDA‑approved NGS assays to confirm FC negativity.sensitivity >=10^-4

Baseline MRD assessment may be required for some techniques; MRD is prognostic and should be incorporated into sequential evaluation.

AML (acute myeloid leukemia): NCCN: perform multiplex gene panels/targeted NGS for management and relapse profiling; MRD is associated with relapse risk but role is evolving; standard NGS may lack MRD sensitivity—use RT‑qPCR or multicolor flow cytometry for MRD assessment and monitor at morphologic remission, around transplantation, and at regimen‑guided intervals.

Assay selection should reflect required sensitivity and clinical context.

CLL (chronic lymphocytic leukemia): NCCN: MRD assessment should use assays with sensitivity of 10^-4 (ERIC standard) or standardized NGS; blood or bone marrow specimens acceptable; FDA‑cleared clonoSEQ can detect to 10^-6 and is referenced for MRD detection.

Revised coverage criteria

Policy revisions clarify coverage for CGP and multigene panels

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

Policy revision effective 02/01/2026 updated CGP coverage indications.

Multigene panels (<=50 genes) revision: Coverage criteria for multigene panels (50 genes or fewer) were revised for use at initial diagnosis and/or recurrence or relapse; an added criterion requires the individual has chronic lymphocytic leukemia for specific coverage pathways.<=50 genes

See policy history for details of revisions.

Optical genome mapping and whole transcriptome sequencing are explicitly identified in the policy as examples of molecular test panels for hematologic cancer that are unproven and not medically necessary. The document states that, due to insufficient evidence of efficacy, “all other molecular test panels for hematologic cancer are unproven and not medically necessary,” and specifically lists optical genome mapping and whole transcriptome sequencing as included in that group.

Current guideline guidance and expert consensus do not support routine MRD testing in chronic lymphocytic leukemia (CLL) outside of clinical trials. The policy cites a NICE briefing and an international expert consensus which note that while undetectable MRD at end of treatment is prognostic and MRD is being actively studied in trials, “current guidelines do not recommend routine MRD testing in practice for CLL at this time,” and use is primarily within research settings.

Guideline panels (ASCO/CCO) conclude there is insufficient evidence to alter maintenance therapy based solely on MRD status. The guideline statements indicate MRD-negative status is associated with improved outcomes but caution that MRD should not be used to guide treatment goals or to change type or duration of therapy outside of clinical trials.

ESMO guidance specific to chronic lymphocytic leukemia indicates that MRD assessment should be carried out within clinical trials to identify complete remission and MRD status, but it is generally not recommended for monitoring after therapy outside of clinical studies at this time.

The policy revision effective 02/01/2026 replaced earlier, narrower wording that limited Comprehensive Genomic Profiling (CGP) coverage to relapsed/recurrent AML. The updated language expands CGP coverage to include individuals with acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasm.

The policy states that all other molecular test panels for hematologic cancer that are not specifically enumerated as proven are considered unproven and not medically necessary. This general exclusion explicitly includes but is not limited to optical genome mapping and whole transcriptome sequencing.

Routine, non-trial MRD testing in CLL currently lacks guideline endorsement and therefore may be considered not medically necessary for routine clinical practice until evidence demonstrates that MRD-directed management improves clinical outcomes outside of research protocols.

The excerpted policy window does not reproduce the full set of explicit “not medically necessary” condition statements. The revision history documents substantive changes to coverage rationale and multigene panel criteria, and notes that portions of the policy not included in this window may contain additional not medically necessary statements or details.

Covered Indications

Acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, myeloproliferative neoplasm for CGP

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

Example CGP tests listed in policy (e.g., FoundationOne Heme).

Acute lymphoblastic leukemia, multiple myeloma, chronic lymphocytic leukemia for multigene panels (<=50 genes) at initial diagnosis/recurrence

Specialist ordering requirement per policy.

Coding and Test Parameters

Applicable/provided codes in policymixed

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.
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 19

1/2

Multigene panel gene count — 50 genes or fewer

ThresholdMultigene panels: 50 genes or fewer

When appliedAt initial diagnosis and/or recurrence or relapse for specified hematologic malignancies (ALL, multiple myeloma, CLL)

Ordering requirementMust be ordered by a hematologist or oncologist for the listed indications

Common MRD sensitivity thresholds referenced — 10^-4, 10^-5, 10^-6

Common sensitivity thresholds10^-4, 10^-5, 10^-6

Example: flow cytometry (MFC)Approximately 10^-4 (0.01%)

Provider Actions and Documentation

Prior Authorization

Ordering step

Multigene panels (≤50 genes) at initial diagnosis and/or recurrence or relapse must be ordered by an appropriate specialist (hematologist or oncologist) and meet the listed clinical indications.

Order multigene panels (≤50 genes) only when a hematologist or oncologist is the ordering provider and the indication matches policy criteria (e.g., ALL, MM, CLL).

Prior Authorization

Potential prior authorization considerations

Payers may require prior authorization or additional documentation for MRD testing, particularly when testing is used to guide treatment decisions outside of clinical trials or when frequency/timing and assay methodology are nonstandard. Consideration may include confirmation that testing is performed in the context of a clinical trial or by a specialized care team following protocolized MRD-guided management.

Prior authorization may be requested when MRD testing is intended to guide changes in therapy outside established trial protocols.
Document trial enrollment or specialized care setting when MRD results will be used to alter therapy (e.g., MRD-SURE approach in MASTER trial).

Not Covered / Unproven Services

Optical genome mapping, whole transcriptome sequencing, and other molecular panels that are not specified as proven are listed in the policy as unproven and not medically necessary. The applicable code list includes codes related to these technologies (for example, CPT-level descriptors and Category I/III codes for whole transcriptome sequencing and optical genome mapping), reinforcing that such tests are considered unsupported for routine coverage when not otherwise proven.

Because guideline groups and expert consensus note that MRD testing in CLL is primarily investigational, the policy indicates routine MRD assessment in CLL performed outside a clinical trial is not recommended by consensus and may be considered unsupported for routine coverage decisions.

The policy provides an informational statement that FDA approval alone is not a basis for coverage. Laboratory regulatory status and FDA-cleared assays are discussed for context, but FDA clearance or approval does not automatically establish medical necessity for coverage determinations.

The current policy text replaces prior, narrower coverage language (for example, CGP limited to relapsed/recurrent AML) with broader CGP coverage statements, but the excerpted window does not explicitly enumerate every test that remains not covered—some exclusions may appear elsewhere in the full policy.

Eligibility Requirements

The policy does not present separate top-level eligibility nodes in the excerpted coverage inventory; eligibility and clinical criteria are specified within the coverage criteria for each test type and indication rather than as standalone, policy-wide eligibility statements.

No additional standalone eligibility requirements are provided in this window; ordering and specialist requirements (for example, hematologist/oncologist ordering for certain multigene panels) are embedded within the coverage criteria and prior authorization sections.

Definitions and Background

Comprehensive Genomic Profiling (CGP) — definition

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

PurposeUsed to characterize hematologic malignancies (e.g., ALL, AML, MDS, MPN) to inform diagnosis, prognosis, and treatment selection.

ExamplesCommercial examples cited: FoundationOne Heme, Neo Comprehensive - Heme Cancers, NEO AML Express.

Measurable Residual Disease (MRD) — definition

DefinitionMeasurable Residual Disease (MRD): a very small number of cancer cells or cell material detectable in the body during or after treatment using sensitive molecular or flow methods.

Use

OpenPayer

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