MA Oncology Testing: Hematologic Malignancy Molecular Diagnostics (Preauthorization Required)
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Governs coverage and medical necessity criteria for molecular diagnostic tests and panels used in evaluation, prognosis, and treatment selection for hematologic malignancies for Blue Cross Blue Shield - Nebraska members; applies to providers requesting preauthorization for these tests.
No material clinical or coverage changes in this revision.
Coverage and Medical Necessity Criteria
Broad RNA Fusion Panels for Hematologic Malignancy
Covered when ALL of the following are met
May be considered reasonable and necessary when the member is undergoing diagnostic workup for adult or pediatric acute lymphoblastic leukemia (ALL).
Broad Molecular Profiling Panels For Hematologic Malignancies and Myeloid Malignancy Panels - Initial testing
Covered when ANY of the following indications applies
Panels performed on bone marrow or peripheral blood.
Repeat Broad Molecular Profiling Panels
Repeat panels may be considered reasonable and necessary when ANY of the following are met
Repeat testing applies to panels performed on bone marrow or peripheral blood.
Broad molecular profiling panels — initial indications
Broad molecular profiling panels and myeloid malignancy panels in bone marrow or peripheral blood may be considered reasonable and necessary when ANY of the following are met:
Supported by policy text.
Broad molecular profiling panels — not reasonable and necessary
Broad molecular profiling panels and myeloid malignancy panels are considered not reasonable and necessary for all other indications.
If a multigene panel is performed, appropriate panel codes should be used; clinical criteria do not address liquid biopsies.
AML focused molecular profiling panels
Acute myeloid leukemia (AML) focused molecular profiling panels may be considered reasonable and necessary when ANY of the following are met:
AML-focused panels are not reasonable and necessary for indications other than AML.
MPN molecular profiling panels
Myeloproliferative neoplasm (MPN) molecular profiling panels may be considered reasonable and necessary when ALL of the following are met:
MPN panels are not reasonable and necessary for other indications.
MRD testing
Measurable (minimal) residual disease (MRD) analysis in bone marrow or peripheral blood may be considered reasonable and necessary when the member has ONE of the following diagnoses and has completed treatment (or a treatment cycle where specified):
MRD methods may include NGS, PCR, or flow cytometry as appropriate per guidelines.
Tumor-specific single-gene and targeted analyses
Tumor-specific single-gene or targeted analyses may be considered reasonable and necessary for the listed indications:
Tumor-specific BCR-ABL1 testing includes kinase domain analysis and qualitative/quantitative assays as clinically indicated.
Includes FISH, qualitative, and quantitative testing as appropriate.
Per NCCN recommendations for initial MPN/MDS workup.
Used for prognostication and treatment planning in AML.
FLT3 testing recommended for prognostic stratification in AML and ALL.
IDH1/2 testing indicated in AML evaluation.
IGHV mutation status informs prognosis and therapy selection in CLL/SLL.
JAK2 testing is part of MPN/MDS evaluation and may be included in panels.
KIT testing indicated for mastocytosis and some AML cases.
MPL testing included in MPN-directed panels.
NPM1 testing recommended in AML workup.
NTRK fusion analysis may be performed by FISH or IHC per guideline guidance.
TP53 sequencing is recommended for prognostic and therapeutic decision-making.
Cytogenetic testing
Cytogenetic testing:
Qualitative FISH and PCR are acceptable methods for PML-RARA detection.
Red blood cell genotyping
Transfusion/genotyping:
Consider baseline RBC phenotype and genotype prior to anti-CD38 therapy to mitigate serologic interference (AABB bulletin updated April 2024).
Covered when consistent with NCCN guidance
Coverage aligned with NCCN guideline–recommended testing for specific hematologic malignancies and indications
See tumor-specific nodes below.
NCCN Myeloproliferative Neoplasms guidance.
NCCN Chronic Myeloid Leukemia guidance.
NCCN Acute Myeloid Leukemia guidance.
NCCN ALL and Pediatric ALL guidance.
NCCN CLL/SLL and B-Cell Lymphomas guidance.
NCCN Multiple Myeloma guidance.
NCCN MRD guidance.
Guideline-concordant testing
Covered when consistent with cited guideline recommendations and medical necessity:
NCCN CLL/SLL guidance.
NCCN Multiple Myeloma guidance.
NCCN AML guidance.
AABB bulletin updated April 2024.
Broad RNA fusion panel tests that use RNA analysis alone and include 51 or more genes are reasonable and necessary only when performed as part of the diagnostic workup for adult or pediatric acute lymphoblastic leukemia (ALL). The policy explicitly states that RNA-only fusion panels meeting the ≥51 gene threshold are considered not reasonable and necessary for all other indications.
Broad molecular profiling panels and myeloid malignancy panels performed on bone marrow or peripheral blood are covered only for the specific indications listed in the policy (see criteria for AML, newly diagnosed ALL, newly diagnosed MDS, suspected MDS with other causes of cytopenia ruled out, suspected MPN when initial genetic evaluation or prior JAK2/CALR/MPL testing is negative, CML with progression to accelerated/blast phase or negative BCR-ABL1 kinase domain mutation analysis, and diffuse large B-cell lymphoma). The policy notes that appropriate multigene panel coding should be used and references NCCN guidance supporting use of multigene NGS panels in selected hematologic malignancies (for example, MPN panels that include JAK2, CALR, and MPL and B‑cell lymphoma panels that include >50 genes).
Within the provided excerpt there are no additional explicit exclusion statements beyond those specifying that certain broad panels are not reasonable and necessary outside the listed indications; the references section and guideline citations do not introduce further named exclusions in this excerpt.
This document excerpt does not list any further explicit exclusions for molecular testing beyond the policy statements that limit coverage to the specified indications and the guideline-aligned recommendations. No additional named exclusions are provided in the cited sections.
Any use of the described broad RNA fusion panels (RNA-only panels with ≥51 genes) or broad molecular profiling/myeloid panels outside the specific indications enumerated in the policy is considered not reasonable and necessary. The policy language makes this limitation explicit for RNA-only fusion panels and for broad molecular/myeloid panels performed on bone marrow or peripheral blood.
All indications for broad molecular profiling panels and myeloid malignancy panels that are not explicitly listed in the policy are considered not reasonable and necessary. The policy directs that multigene panels be coded appropriately and clarifies that these clinical criteria do not address liquid biopsy testing.
In the provided document chunks there are no explicit statements framed with the phrase 'not medically necessary' beyond the policy’s clear descriptions that certain broad panels are not reasonable and necessary outside the listed indications. The NCCN guideline citations support where multigene testing is appropriate but do not add separate 'not medically necessary' phrasing in these excerpts.
This excerpt does not contain any additional explicit statements labeled 'not medically necessary.' The policy instead uses the term 'not reasonable and necessary' to describe coverage limits for broad RNA fusion and broad molecular/myeloid panels when used outside specified indications.
Procedure and Billing Codes
| 81456 | Molecular profiling panels - example listed in reference table |
| 81450 | Targeted gene panel, example in reference table |
| 81455 | Targeted gene panel, example in reference table |
| 81170 | ABL1 kinase domain analysis |
| 0364U | ClonoSEQ Tracking (MRD) Assay |
| 0016U | BCR/ABL1 RNA Quantitative with Interpretation |
| 0040U | MRDx BCR-ABL Test |
| 81219 | CALR mutation analysis |
| 81218 | CEBPA mutation analysis / related assays |
| 81206 | Example cytogenetic/molecular test codes listed |
| affected codes | Appropriate multigene panel codes should be used when a multigene panel is performed (document notes panels should be coded appropriately). |
| affected codes | Placeholder — specific CPT/HCPCS codes are not provided in these chunks |
| 0001U | RBC DNA HEA 35 AG 11 BLD GRP WHL BLD CMN ALLEL |
| 0016U | ONC HMTLMF NEO RNA BCR/ABL1 BLD/BNE MARROW |
| 0017U | ONC HMTLMF NEO JAK2 MUTATION DNA BLD/BNE MARROW |
| 0023U | ONC AML DNA GNTYP INT TANDEM DUP DETCJ/NONDETCJ |
| 0027U | JAK2 GENE ANALYSIS TRGT SEQ ALYS EXONS 12-15 |
| 0040U | BCR/ABL1 GENE TLCJ ALYS MAJOR BP QUANTITATIVE |
| 0046U | FLT3 GENE INT TANDEM DUPL VARIANTS QUANTITATIVE |
| 0049U | NPM1 GENE ANALYSIS QUANTITATIVE |
| 0050U | TRGT GEN SEQ ALYS AML 194 GENE INTERROG SEQ VRNT |
| 0171U | TARGETED GENOMIC SEQUENCE ALYS PNL DNA 23 GENES |
Prior Authorization, Documentation, and Operational Notes
Obtain prior authorization (policy-level)
Preauthorization is required for hematologic malignancy molecular diagnostic testing under this policy; when applicable, CMS national or local coverage determinations (NCD/LCD) take precedence.
Prior authorization required for broad and myeloid panels
Obtain prior authorization before performing broad molecular profiling panels, myeloid malignancy panels, or listed single-gene/focused panels on bone marrow or peripheral blood when used for the policy-specified indications.
Policy requires preauthorization for hematologic molecular diagnostics
The policy title and content indicate preauthorization is required for hematologic malignancy molecular diagnostics; follow the insurer's prior authorization process for tests covered by this policy.
Prior authorization required for listed CPT/PLA codes
Submit prior authorization for the specific molecular pathology and genomic procedure codes listed in the policy reference tables before testing.
Allow stepwise testing or NGS panel for MPN
NCCN guidance allows either stepwise testing or an NGS multigene panel that includes JAK2, CALR, and MPL for suspected MPN; providers may follow stepwise testing or order an NGS panel that includes these genes.
- For suspected MPN, panel must include at minimum JAK2, CALR, and MPL per policy (chunk 21).
Pre-test counseling and coding guidance
Discuss with patients the potential for incidental germline findings before performing somatic mutation profiling and ensure coding reflects the performed multigene panel when applicable.
- Inform patients that somatic testing can uncover clinically relevant germline variants (chunk 5).
- If a multigene panel is performed, use appropriate panel CPT codes as noted in the policy (chunks 6 and 19).
Use appropriate panel CPT codes; liquid biopsies not addressed
When a multigene panel is performed, bill using the appropriate multigene/panel CPT code; note that the clinical criteria do not address liquid biopsies.
- Policy note: 'If a multigene panel is performed, appropriate panel codes should be used.' (chunk 19).
- Reference table lists example panel codes (chunk 6).
Follow recommended laboratory methods and document intent
When indicated by NCCN or test-specific guidance, use quantitative or qualitative RT-PCR, FISH, or multiplex RT-PCR for assays such as BCR-ABL1 and document diagnostic intent and monitoring implications.
- NCCN recommends evaluation for BCR-ABL1 via FISH or multiplex RT-PCR and quantitative RT-PCR for monitoring (chunk 44).
Consider baseline RBC genotyping before anti‑CD38 therapy
Consider baseline red blood cell phenotype and genotype prior to initiating anti‑CD38 monoclonal antibody therapy; document the clinical rationale to support testing.
- AABB bulletin (updated April 2024) recommends consideration of baseline phenotype/genotype to mitigate anti‑CD38 interference with serologic testing (chunk 57).
Denial risk: unsupported use of ≥51‑gene RNA fusion panels
Do not perform broad RNA fusion panels with 51 or more genes using RNA analysis alone for indications other than diagnostic workup for adult or pediatric ALL; such uses are considered not reasonable and necessary and may be denied.
- Policy: 'RNA fusion panel tests with 51 or more genes utilizing RNA analysis alone ... may be considered reasonable and necessary when: the member is undergoing diagnostic workup for adult or pediatric ALL.' (chunk 17).
- Policy: '... are considered not reasonable and necessary for all other indications.' (chunk 17).
Denial risk for panels ordered outside listed indications
Broad molecular profiling panels and myeloid malignancy panels performed for indications not explicitly listed in the policy are considered not reasonable and necessary and are at risk for denial.
- Policy: 'Broad molecular profiling panels ... are considered not reasonable and necessary for all other indications.' (chunk 19).
Verify procedure/diagnosis code pairs with Quick Code Search
Use the Quick Code Search tool to check whether a procedure/diagnosis code pair is listed and how it will be adjudicated prior to submission; code-pair lookup may indicate approval, denial, or review.
- Quick Code Search instructions: enter procedure code then diagnosis code to see if the pair will be approved, denied, or held for review (chunk 58).
No insurer step therapy sequencing specified
No formal step therapy sequencing is described in this excerpt; specific step therapy requirements are not provided. The policy emphasizes baseline testing prior to anti‑CD38 therapy rather than sequencing of molecular tests.
- Policy states NCCN allows stepwise testing for MPN but does not prescribe insurer step therapy sequencing (chunk 36).
- Policy notes baseline RBC genotyping recommendation before anti‑CD38 therapy (chunk 57).
Operational denial triggers not provided in excerpt
Operational denial triggers and detailed prior‑authorization workflows are not specified in the provided excerpt; follow the insurer's published prior authorization process and the policy's coverage criteria when submitting requests.
Key Terms and Definitions
Line of Therapy Context
salvage
Line of therapy: salvage.
salvage
Line of therapy: salvage; supports repeat testing scenarios.
salvage
Line of therapy: salvage; NCCN CML guidance.
first-line
Line of therapy: first-line; NCCN AML guidance.
first-line
Line of therapy: first-line; NCCN and AABB guidance.
Required and Recommended Biomarkers
Clinical Context and Rationale
Molecular diagnostic testing in hematologic malignancies is used to identify biomarkers for diagnosis, prognosis, therapy selection, and monitoring; guideline citations (NCCN) are referenced to align coverage with recommended testing strategies. The policy highlights examples where multigene NGS panels are appropriate (for instance, MPN panels that include JAK2, CALR, and MPL or B‑cell lymphoma panels with at least >50 genes), and it notes that stepwise testing is an acceptable alternative when indicated by guidelines.
Policy Revision Timeline
Policy M.77 (Hematologic Malignancy Molecular Diagnostics) became effective.
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