Please refer to CMS website for the most current applicable:

• CMS Online Manual System (IOMs)
• National Coverage Determination (NCD)
• Local Coverage Determination (LCD)
• Local Coverage Article (LCA)
• Transmittals

Genetic Testing for Hematologic Malignancies and Suspected Myeloid Disorders

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ID Number

Medicare Administrative Contractors (MACs)

Applicable States/Territories

• NCD Next Generation Sequencing (NGS) - 90.2
• icp MoIDX: Genetic Testing for BCR-ABL Negative Myeloproliferative Disease MoIDX: Next-Generation Sequencing Lab-Developed Tests for Myeloid Malignancies and Suspected Myeloid Malignancies - 136815, 138176 - 16, 18-Wisconsin Physicians Service Insurance Corporation - IA, IN, KS, MI, MO, NE
• LCD LCA Genomic Sequence Analysis Panels in the Treatment of Hematolymphoid Diseases Molecular Pathology Procedures | Billing and Coding: Molecular Pathology Procedures - 137606, L35000, AS56199 - CG National : Services, Inc. - CT, IL, MA, ME, MN, NH, NY, RI, VT, WI
• LCD MoIDX: Genetic Testing for BCR-ABL Negative Myeloproliferative Disease MoIDX: Next-Generation Sequencing Lab-Developed Tests for Myeloid Malignancies and Suspected Myeloid Malignancies - L36117, L38070 - J15 - CGS Administrators, - KY, OH
• LCD MolDx: Genetic Testing for BCR-ABL Negative Myeloproliferative Disease MolDx: Next-Generation Sequencing Lab-Developed Tests for Myeloid Malignancies and - L36180, L38123 - JE - Noridian Healthcare Solutions, LLC - CA, HI, NV, American Samoa, Guam, Northern Mariana Islands

MolDX: Next-Generation Sequencing Lab-Developed Tests for Myeloid Malignancies and Suspected Myeloid Malignancies

LCD MolDX: Genetic Testing for BCR-ABL Negative Myeloproliferative Disease - L36186

JF - Noridian Healthcare Solutions, LLC

AK, AZ, ID, MT, ND, OR, SD, UT, WA, WY

Genetic Testing for Hematologic Malignancies and Suspected Myeloid Disorders

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MolDX: Next-Generation Sequencing Lab-Developed Tests for Myeloid Malignancies and Suspected Myeloid Malignancies

• LCD Biomarkers for Oncology - 135396 - Palmetto GBA - AR, CO, D.C., DE, MD, NJ, NM, OK, PA, TX, LA, MS
• Leb MolDX: Genetic Testing for BCR- ABL Negative Myeloproliferative Disease MolDx: Next-Generation Sequencing Lab-Developed Tests for Myeloid Malignancies and Suspected Myeloid Malignancies | L36044, L38047 | JJ, JM - Palmetto GBA | AL, GA, NC, SC, TN, VA, WV
• LCD Molecular Pathology Procedures | L34519 | JN - First Coast Service Options, Inc. | FL, PR, U.S. VI

Description

Genetic testing can be utilized to diagnose and monitor cancer indications including, but not limited to, leukemia, lymphoma, myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPNs). This type of testing is indicated for an individual who exhibits disease symptoms and may be necessary to diagnose or rule out suspected cancer or monitor known cancer.

Comprehensive genomic profiling (also referred to as comprehensive molecular profiling) is a type of test that involves a combination of laboratory methodologies to detect genetic alterations and biomarkers in blood or bone marrow to aid in the management of hematologic malignancies and suspected myeloid disorders. Testing is performed by removing a small sample of tissue for evaluation (e.g., bone marrow biopsies, bone marrow aspirates, bone marrow clots), blood draw (peripheral blood samples), or sites located outside of the bone marrow (extramedullary) suspected of harboring a myeloid malignancy.

Techniques can vary from test to test and may include but are not limited to, next-generation sequencing (NGS), fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Examples of comprehensive genomic profiling tests include, but are not limited to, FoundationOne Heme and Neogenomics myeloid and/or heme panels.

Multigene (or expanded) panels analyze a broad set of genes simultaneously (as opposed to single gene testing that searches for variants in one specific gene). Panels often include medically actionable genes but may also include those with unclear medical management. Targeted (or focused) multigene panels analyze a limited number of genes targeted to a specific condition.

Single gene testing may also be performed for hematologic malignancies and suspected myeloid disorders and may be indicated for an individual who exhibits disease symptoms and may be necessary to diagnose or rule out suspected cancer or monitor known cancer. These include, but are not limited to, ASXL1, CEBPA, FLT3, IDH1, IDH2, KIT, MYD88, NPM1, NRAS, RUNX1, SF3B1, SRSF2, TP53, U2AF1 and ZRSR2.

JAK2 V617F variant analysis is another single gene laboratory test used to assist in the diagnosis of myeloproliferative neoplasms (MPNs) which are a group of conditions characterized by an overproduction of specific types of blood or fiber cells in the bone marrow. MPNs include essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF).

• ET is characterized by an overproduction of platelets due to a clonal process and may be suspected when an individual’s platelet count is at least 450 x 10⁹/L.2,79
• PV is differentiated from the other MPNs by the indication of increased red blood cell volume. An individual with the following laboratory results may require further evaluation with genetic testing: elevated red cell mass greater than 25% above the mean normal predicted value and/or elevated hemoglobin (greater than 16.5 g/dL for men or greater than 16 g/dL for women) and/or increased hematocrit (greater than 49% for men and greater than 48% for women).2,79
• PMF is defined by the existence of bone marrow fibrosis that is not linked to another myeloid disorder such as chronic myeloid leukemia (CML), PV, ET or myelodysplastic syndromes (MDS). An individual with an increased white cell count (greater than 11 x 10⁹/L) may require additional assessment.2,79

Laboratory results for ET, PV and PMF remain persistent over time (typically a 4-month duration) and other reasons for the unexplained laboratory values, such as medications (including testosterone), dehydration and personal habits (eg, alcohol consumption), should be eliminated as a cause.79

CALR and MPL gene analysis is warranted if an individual receives a negative JAK2 V617F result. CALR and MPL variants are detected in an individual diagnosed with ET or PMF but not in an individual with PV.

Coverage Determination

Humana follows the CMS requirements that only allows coverage and payment for services that are reasonable and necessary for the diagnosis and treatment of illness or injury or to improve the functioning of a malformed body member except as specifically allowed by Medicare.

Genetic tests must demonstrate clinical utility, analytical and clinical validity and fulfill the CMS “reasonable and necessary” criteria. Analytic validity (test accurately identifies the gene variant), clinical validity (test identifies or predicts the clinically defined disorder) and clinical utility (test measurably improves clinical outcomes) of the genetic test is supported by generally accepted standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, specialty society recommendations, and views of physicians practicing in relevant clinical areas.

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The test must be ordered by a physician who is treating the beneficiary and the results will be used in the management of a beneficiary’s specific medical problem.

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For jurisdictions with no Medicare guidance for a particular test, Humana will utilize the MolDX program and Technical Assessments for molecular assays as the standard to evaluate clinical utility, analytical and clinical validity in conjunction with adhering to Medicare’s reasonable and necessary requirement.

In interpreting or supplementing the criteria above and in order to determine medical necessity consistently, Humana may consider the following criteria:

Comprehensive Genomic Profiling or Multigene Panel Testing for Hematologic Malignancies and Suspected Myeloid Disorders

Comprehensive genomic profiling or multigene panel testing (eg, 81450, 81451, 81455, 81456) will be considered medically reasonable and necessary for hematologic malignancies and suspected myeloid disorders when the following requirements are met:

• A multigene panel is defined as a test that analyzes more than one gene simultaneously. A panel will be considered medically reasonable and necessary if more than one gene impacts the clinical management of the individual being tested. The panel must evaluate genes and/or alleles in accordance with the panel’s indicated use; AND
• Testing is performed by removing a small sample of tissue for evaluation (eg, bone marrow biopsies, bone marrow aspirates, bone marrow clots), blood draw (peripheral blood samples), or sites located outside of the bone marrow (extramedullary) suspected of harboring a myeloid malignancy;10,11,12,13,14 AND
• Clinical, laboratory and pathologic assessment are nondiagnostic (such as demonstration of persistent cytopenias [eg, four months] by complete blood count, microscopic examination of a bone marrow biopsy and bone marrow cytogenetic studies.

Other than the clinical feature of the number of cytopenias and specific cytogenetic changes found recurrently in myelodysplastic syndrome [MDS], all other diagnostic criteria in MDS rely upon light microscopy findings);

• AND one of the following:
  1. Cancer of the blood and bone marrow (eg, acute myelogenous leukemia [AML]); 10,11,12,13,14 OR
  2. MDS;10,11,12,13,14 OR
  3. Myeloproliferative neoplasms (MPNs) which include polycythemia vera (PV), essential thrombocythemia (ET) or primary myelofibrosis (PMF); 10,11,12,13,14 OR
  4. For an individual that does not have a diagnosis of cancer but a myeloid malignancy but is suspected;10,11,12,13,14 AND
     • Undefined cytopenia for greater than four months without a known cause; 10,11,12,13,14 AND
     • Other possible causes have been reasonably excluded10,11,12,13,14

Single Gene Testing

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ABL1 gene analysis will be considered medically reasonable and necessary for any of the following indications to guide therapeutic decision making:

• Acute lymphoblastic leukemia (ALL);3,15 OR
• Chronic myeloid leukemia (CML)3,15

ASXL1 gene analysis (81175/81176) will be considered medically reasonable and necessary for any of the following indications:

• AML (includes acute promyelocytic leukemia [APL]);3 OR
• Chronic myeloid leukemia (CML);62 OR
• MDS;3 OR
• MPNs;3 OR
• Systemic mastocytosis;67 OR
• Undefined cytopenia for greater than four months without a known cause 10,11,12,13,14

BCR/ABL gene analysis will be considered medically reasonable and necessary for any of the following indications:

• Evaluation of CML or BCR-ABL positive ALL suboptimal response to initial tyrosine kinase inhibitor therapy or loss of response to tyrosine kinase inhibitor therapy;15 OR
• Suspected CML with either persistent, unexplained leukocytosis or thrombocytosis15
• MPNs3

Services that do not meet the criteria above are not medically necessary and thus do not provide a clinical benefit. Medically unnecessary services carry risks of adverse outcomes and may interfere with the pursuit of other treatments which have demonstrated efficacy.

Coverage Limitations

US Government Publishing Office. Electronic code of federal regulations: part 411 – 42 CFR § 411.15 - Particular services excluded from coverage

• Tests considered screening in the absence of clinical signs and symptoms of disease that are not specifically identified by the law;68 OR
• Tests that confirm a diagnosis or known information;68 OR
• Tests to determine risk for developing a disease or condition;68 OR
• Tests performed to measure the quality of a process;68 OR

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• Tests without diagnosis specific indications;68 OR
• Tests identified as investigational by available literature and/or the literature supplied by the developer and are not a part of a clinical trial68

These treatments and services fall within the Medicare program’s statutory exclusion that prohibits payment for items and services that have not been demonstrated to be reasonable and necessary for the diagnosis and treatment of illness or injury (§1862(a)(1) of the Act). Other services/items fall within the Medicare program’s statutory exclusion at 1862(a)(12), which prohibits payment.

The following items will not be considered medically reasonable and necessary:

• Genetic tests that have not demonstrated clinical utility, analytical and clinical validity via the MolDX Program

A review of the current medical literature shows that the evidence is insufficient to determine that these services are standard medical treatments. There remains an absence of randomized, blinded clinical studies examining benefit and long-term clinical outcomes establishing the value of these services in clinical management.