BCBS Rhode Island MRD Testing Coverage & Prior Auth

Coverage Criteria for MRD Testing

Medical Necessity Criteria for MRD Detection

Covered when ALL of the following are met for Medicare Advantage and Commercial Products (as applicable):

Top-level: All numbered conditions 1-10 must be satisfied for medical necessity when detecting MRD using named tests

From policy list of criteria

NGS test applicability: If NGS methodology is used, then either the Somatic (A) or Germline (B) branch must be met (or NGS not applicable if patient does not meet definitions below).

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A. Somatic (Acquired) Cancer: Patient has either recurrent, relapsed, refractory, metastatic, or advanced stage III or IV cancer; has not been previously tested with the same NGS test for the same cancer genetic content; and has decided to seek further cancer treatment (e.g., therapeutic chemotherapy).

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A.II NGS lab requirements: The diagnostic laboratory test using NGS must have FDA approval or clearance as a companion in vitro diagnostic, must have an FDA-approved/cleared indication for use in that patient’s cancer, and results must be provided to the treating physician using a report template that specifies treatment options.

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B. Germline (Inherited) Cancer: Patient has ovarian or breast cancer; there is a clinical indication for germline (inherited) testing for hereditary breast/ovarian cancer; patient has a risk factor for hereditary breast/ovarian cancer; and patient has not been previously tested with the same germline NGS test for the same germline content.

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Clinical intended-use and population: Patient has a personal history of cancer within the intended use of the MRD test; identification of recurrence or progression by the test is recognized in NCCN or other established guidelines as prompting a definitive change in management; and the test is being used in the population in which it was analytically validated and according to intended use.

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Lead-time and performance: The test must demonstrate detection of molecular recurrence or progression before clinical/biological/radiographical evidence and demonstrate sensitivity and specificity for subsequent recurrence/progression comparable with or superior to radiographical or other standard-of-care methods for the cancer type.

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Therapeutic monitoring validity: If used for monitoring a specific therapeutic response, the test must demonstrate clinical validity in the published literature for the explicit management or therapy indication.

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Technical assessment requirement: Except for FDA-approved, established standard-of-care single-gene PCR tests, MRD tests must satisfactorily complete a technical assessment demonstrating analytical validity, clinical validity, and clinical utility per policy to be considered reasonable and necessary.

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Equivalence to accepted standards: Tests utilizing similar methodology or evaluating similar analytes to an accepted standard must demonstrate equivalent or superior performance (sensitivity and/or specificity) for the same indication in the same intended-use population.

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Test-specific coverage

Specific coverage statements for named tests when criteria met:

Hematologic malignancy MRD: clonoSEQ may be considered medically necessary for Acute Lymphoblastic Leukemia (ALL), Multiple Myeloma (MM), Chronic Lymphocytic Leukemia (CLL), and Diffuse Large B-Cell Lymphoma (DLBCL) when policy criteria are met.

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Named ctDNA tests: Guardant REVEAL and Guardant Response may be considered medically necessary when the medical necessity criteria for MRD detection in this policy are satisfied.

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Covered clinical indications for MRD testing

Covered when testing meets disease-specific indications and assay appropriateness per clinical guidelines (NCCN, ELN) and when associated criteria for sensitivity or target are met.

Hematologic malignancy MRD coverage: MRD testing is supported and routinely assessed for specific hematologic conditions when appropriate, validated molecular targets or assays are available (examples: RT-qPCR for BCR-ABL1 in CML; PCR/RT-qPCR for NPM1, PML-RARA, RUNX1-RUNX1T1, CBFB-MYH11 in AML/APL; IgH/TCR clonality testing or NGS-based assays in ALL, MM, CLL, and lymphomas). Assay selection should match target stability and required sensitivity.BCR-ABL1 qPCR sensitivity requirement: IS <= 0.0032% (MR4.5) and turnaround < 2 weeks

PCR-based assays historically have superior sensitivity for some AML targets; FLT3-ITD is noted as not appropriate for MRD due to instability.

Lymphoma MRD usage

Covered when used for surveillance and risk stratification in lymphomas with validated ctDNA assays.

Lymphoma ctDNA MRD coverage: ctDNA MRD testing may be used for disease burden assessment, prognostication, monitoring for relapse, and to support risk-adapted therapy decisions in B-cell lymphomas where validated assays exist. Serial monitoring is recommended because patients may convert from ctDNA-negative to positive over time.ctDNA tests should demonstrate clinical validity and high sensitivity compared to imaging (lead time 3-6 months reported)

Use may reduce surveillance imaging frequency and enable pre-emptive or risk-adapted interventions in select study settings.

Coverage for genetic testing services described in this policy may be limited or excluded for certain commercial self‑funded employer groups that have contract exclusions related to the state biomarker testing mandate. Providers should consult the member's Benefit Booklet, Evidence of Coverage, or Subscriber Agreement to determine whether the member's plan includes such exclusions and whether prior authorization or alternative coverage rules apply.

MRD testing is not appropriate when the molecular target is known to be unstable or unreliable for longitudinal monitoring (for example, FLT3‑ITD in AML) or when the specimen is unlikely to contain sufficient circulating tumor DNA for detection (such as small or less aggressive tumors). Additionally, ctDNA‑based MRD assays cannot detect a second primary tumor and may yield discordant results with tissue due to tumor heterogeneity or sampling time differences.

This policy sets forth medical necessity criteria and coverage guidance but does not guarantee that any individual claim will be paid. Benefits and eligibility are governed by the member's subscriber agreement, member certificate, or employer agreement, which supersede this policy. For member‑specific benefit questions, providers should contact the provider call center.

When MRD testing uses NGS or when no specific CPT code exists, the test must complete the required technical assessment (TA) demonstrating analytical validity, clinical validity, and clinical utility unless the test is an FDA‑approved single‑gene PCR standard‑of‑care. Prior authorization is required for Medicare Advantage and recommended for Commercial Products; unlisted genetic testing CPT codes (including 81479) require prior authorization to determine the service rendered and medical necessity. Laboratories that provide services without authorization may have those services denied and be financially liable.

Age‑related clonal hematopoiesis of indeterminate potential (CHIP) can introduce somatic variants into peripheral blood that are not tumor‑derived and may confound ctDNA MRD testing. Without mitigation strategies such as paired peripheral blood cell controls or validated bioinformatic filtering, ctDNA MRD results can be misclassified, potentially leading to inappropriate clinical decisions.

Services determined to be not medically necessary under this policy, or services that fall outside a member's covered benefits, may not be covered and could result in financial liability to the member. Prior written consent may be required if a provider intends to bill the member for non‑covered services. Policy availability does not substitute for verification of prior authorization or member benefits.

Indications and Use Cases Considered Medically Necessary

Detection/monitoring of MRD in patients with a personal history of cancer

Detection/monitoring of MRD in patients with a personal history of cancer within the test's intended use (named tests may be considered medically necessary when policy criteria are met).

Covered indications - general: MRD testing may be used to detect or monitor MRD in patients with a personal history of cancer when the test is used within its intended population and meets policy medical necessity criteria. Named assays (e.g., clonoSEQ, Guardant REVEAL, Guardant Response) may be considered medically necessary if all policy criteria are satisfied.

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MRD testing for disease-specific molecular targets

MRD testing for disease-specific molecular targets and validated assays (ctDNA or marrow-based) is covered when assay selection and performance match the clinical indication.

Disease-specific molecular targets: MRD testing is covered for established molecular targets and methodologies such as BCR-ABL1 in CML; NPM1, PML-RARA, and CBF fusions in AML/APL; and IgH/TCR clonality or validated NGS assays in lymphoid malignancies. Assay selection must consider target stability (e.g., avoid unstable targets such as FLT3-ITD for MRD) and required sensitivity for clinical decision-making.

CPT and Diagnosis Codes

Named MRD test CPT/CodesCPT

0364U	clonoSEQ (Adaptive Biotechnologies)
81479	Guardant REVEAL (Guardant Health)
0422U	Guardant Response (Guardant Health)

Unlisted / miscellaneous genetic testing CPTCPT

Unlisted CPT

Use Unlisted CPT when no specific CPT code exists for the genetic testing service

Covered CPT Codes (pan-solid tumor cfDNA response)CPTCovered

0422U

Oncology (pan-solid tumor), analysis of DNA biomarker response to anti-cancer therapy using cell-free circulating DNA, biomarker comparison to a previous baseline pre-treatment cell-free circulating DNA analysis using next-generation sequencing, algorithm reported as a quantitative change from baseline, including specific alterations, if appropriate (Guardant Response) (New code effective 1/01/2024)

Covered CPT Codes (hematolymphoid MRD)CPTCovered

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 (clonoSEQ) (New Code Effective 4/1/2023)

Unlisted CPT requiring prior authorizationCPT

81479

Unlisted molecular pathology procedure (requires prior authorization for Medicare Advantage Plans and Commercial Products)

ICD-10 Diagnosis Codes associated with covered MRD testingICD-10

C83.30 - C83.39	Non-Hodgkin lymphoma diagnosis codes (as listed)
C90.00 - C90.02	Multiple myeloma diagnosis codes (as listed)
C91.00 - C91.02	Lymphoid leukemia diagnosis codes (as listed)
C91.10 - C91.12	Other lymphoid leukemia diagnosis codes (as listed)
Z85.6	Personal history of other malignant neoplasm of lymphoid, hematopoietic and related tissue
Z85.79	Personal history of other malignant neoplasm of unspecified site

BCR-ABL1 molecular response threshold

Molecular response thresholdBCR-ABL1 international scale (IS) ≤ 0.0032% (designated MR4.5)

Turnaround time expectationTime to results: less than 2 weeks

Clinical useRequired sensitivity and rapid turnaround support decisions such as TKI discontinuation, therapy change, or HSCT referral

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior authorization and benefit verification

Prior authorization is required for Medicare Advantage plans and recommended for Commercial Products. Providers must verify member-specific benefits and obtain any required prior authorization via the payer’s online tool or provider call center before performing testing. Policy availability does not guarantee payment; benefits and eligibility are determined by the member's subscriber agreement/certificate and/or employer agreement.

Prior authorization required for Medicare Advantage; recommended for Commercial Products.
Obtain prior authorization via the online tool for participating providers or call the provider call center for member-specific benefit verification.
Policy availability is informational only and does not guarantee payment; verify eligibility/benefits prior to service.

Prior Authorization

Prior authorization required for unlisted CPT

Use of an unlisted molecular pathology CPT code (81479) requires prior authorization for Medicare Advantage and Commercial Products to determine the exact service being rendered and whether it is covered or medically necessary. Submit supporting documentation as part of the authorization request.

Eligibility Requirements

No additional top‑level eligibility nodes are defined in this section of the policy. Eligibility for MRD testing is determined by satisfying the medical necessity criteria and by reviewing the member's specific benefits and contract terms.

There are no separate family‑history or other prerequisite eligibility nodes documented for MRD testing in this policy. Clinical indication and adherence to the stated coverage criteria guide eligibility.

The policy does not list additional standalone prior‑testing or sequencing requirements as top‑level eligibility conditions; instead, prior testing considerations are embedded within the medical necessity criteria (for example, not previously tested with the same NGS test for the same genetic content).

Services Not Covered

Tests that have not completed the required technical assessment (when applicable) or tests excluded by a group's contract exclusions for genetic testing are not covered for members subject to those exclusions. Additionally, laboratory services provided without required authorization may be denied and treated as the financial responsibility of the performing laboratory.

MRD testing that relies on unstable molecular targets (for example, FLT3‑ITD in AML) is not covered because such targets may change at relapse and are unsuitable for longitudinal MRD monitoring. Similarly, ctDNA MRD testing performed without strategies to mitigate confounding from CHIP (such as paired peripheral blood controls or validated filtering) is not covered due to risk of misclassification.

Definitions and Key Terms

Minimal (or measurable) residual disease testing uses molecular assays to detect tumor‑derived genetic material at very low levels to monitor for residual disease, recurrence, or response to therapy. MRD assays may establish a tumor‑specific baseline from diagnostic material and then use minimally invasive specimens (blood or bone marrow) for serial monitoring. Modalities include single‑gene RT‑qPCR, targeted PCR assays, flow cytometry, cytogenetics, and NGS‑based approaches (including ctDNA).

Measurable (Minimal) Residual Disease testing

DefinitionMeasurable (Minimal) Residual Disease (MRD) testing: molecular assays detecting tumor-derived material to diagnose progression, recurrence, or monitor response

Specimen typesMay use tumor diagnostic material to establish baseline and minimally invasive specimens (plasma or bone marrow) for serial monitoring

Primary purposesDetect recurrence/progression earlier than clinical/radiographic evidence; measure tumor response to therapy

Standard-of-care PCR-based MRD tests

Background and Rationale

MRD testing is intended to detect molecular evidence of residual cancer cells before clinical or radiographic recurrence and to guide management decisions. For hematologic malignancies, established targets (for example, BCR‑ABL1 in CML and NPM1/PML‑RARA/CBF fusions in AML) have well‑defined roles. ctDNA (circulating tumor DNA) assays provide a noninvasive option for serial monitoring in selected solid tumors and lymphomas but require sufficient tumor shedding, validated assay sensitivity, and strategies to address confounders such as CHIP. Appropriate assay selection should match the target stability and required sensitivity for the intended clinical use.

OpenPayer

Minimal Residual Disease (MRD) Testing for Cancer