Humana Molecular Diagnostic Assays and Breath Testing for Transplant Rejection - Medicare Advantage Form

Please refer to CMS website for the most current applicable National Coverage Determination (NCD)/ Local Coverage Determination (LCD)/Local Coverage Article (LCA)/CMS Online Manual System/Transmittals.

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Medicare Administrative Contractors (MACs)

Applicable States/Territories

• NCD: Heartsbreath Test for Heart Transplant Rejection
• LCD LCA: MolDx: Molecular Diagnostic Tests (MDT) Billing and Coding: MoIDX: Molecular Diagnostic Tests (MDT) MoIDX: Molecular Testing for Solid Organ Allograft Rejection Affected Codes: L36807 AS57772, L38680 Contractor/Region: J5 —J8 Wisconsin Physicians Service Insurance Corporation States: IA, IN, KS, MI, MO, NE
• Billing and Coding: MolDX: Molecular Testing for Solid Organ Allograft Rejection Affected Code: A58207
• LCD LCA: MolDX: Molecular Testing for Solid Organ Allograft Rejection Billing and Coding: MolDX: Molecular Testing for Solid Organ Allograft Rejection MolDx: Molecular Diagnostic Tests (MDT) Affected Codes: L38582, A58061, L36021 Contractor/Region: J15 - CGS Administrators, LLC (Part A/B MAC) States: KY, OH
• LCD LCA: MolDX: Molecular Testing for Solid Organ Allograft Rejection Billing and Coding: MolDX: Molecular Testing for Solid Organ Allograft Rejection Affected Codes: L38629, A58168 Contractor/Region: JE - Noridian Healthcare Solutions States: CA, HI, NV, American Samoa, Guam, Northern Mariana Islands

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Tests (MDT)

• TCP: Diagnostic Billing and Coding: MolDX: Molecular Diagnostic Tests (MPT) Affected Codes: L36256, AS7527 Contractor/Region: JF - Noridian States: AK, AZ, ID, MT, ND,
• LCA: MolDX: Molecular Testing for Solid Organ Allograft Rejection Billing and Coding: MolDX: Molecular Testing for Solid Organ Allograft Rejection Affected Codes: 138671, AS58170 Contractor/Region: Healthcare Solutions, LLC States: OR, SD, UT, WA, WY
• LCD LCA: MolDX: Molecular Diagnostic Tests (MDT) Billing and Coding: MolDX: Molecular Diagnostic Tests (MDT) Affected Codes: L35025, A56853 Contractor/Region: JJ - Palmetto GBA (Part A/B MAC) JM - Palmetto GBA States: AL, GA, NC, SC, TN, VA, WV
• Billing and Coding: MolDX: Molecular Testing for Solid Organ Allograft Rejection Affected Codes: L38568, A58019

DescriptionA biopsy is considered the gold standard for the diagnosis of organ transplant rejection. There are no specific laboratory findings that can accurately diagnose acute rejection. Organ biopsy is required to differentiate between T-cell mediated rejection (TCMR) and antibody mediated rejection (ABMR), to accurately grade the severity of rejection, and to determine the degree of organ damage. Biopsy of the allograft organ can also reveal other causes of inflammation and injury. Noninvasive methods for the detection and surveillance of transplant rejection have been developed with the goal of reducing the number of biopsies. These tests include, but may not be limited to, the following:Gene Expression Profiling • A gene expression test (eg, AlloMap) has been developed to predict the likelihood of cardiac rejection. Following a transplant, the test evaluates the quantitative measure of 20 genes using an algorithm to report a rejection risk score.

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The test is intended to be used in conjunction with standard clinical assessment to aid in the identification of heart transplant recipients with stable allograft function who have a low probability of moderate/severe acute cellular rejection at the time of testing.

• Immune response gene expression panel (eg, nCounter Human Organ Transplant Panel) has been developed to assess immune response following organ transplant utilizing a panel of 770 genes across 37 pathways that purportedly evaluates kidney, heart, liver and lung rejection.
• Messenger deoxyribonucleic acid (mDNA) and Messenger ribonucleic acid (mRNA) gene expression utilize proprietary microarrays and algorithms based on a reference set of biopsies to provide scores to assess the probability of rejection by reportedly measuring cell-mediated rejection. The tests are purportedly utilized for heart, kidney and lung transplants. Examples of mDNA and mRNA gene expression assays include, but may not be limited to:
  • Clarava pretransplant mRNA expression assay
  • Molecular Microscope Diagnostic system (eg, MMDx Heart, MMDx Kidney, MMDx Lung)
  • TruGraf Blood Gene Expression Test
  • Tutivia post-transplant mRNA expression assay
• Molecular gene expression assay (eg, Kidney Solid Organ Response Test [kSORT]) has been developed for kidney transplant rejection to reportedly detect individuals who are at high risk for acute rejection. Polymerase chain reaction (PCR) is utilized to measure the relative messenger ribonucleic acid (mRNA) expression levels of 17 genes that have been known to be associated with acute rejection. Individuals are classified into high, low or indeterminate risk according to a correlation-based algorithm.
• Antigen-Specific T-cell Function Assay
  • CD154+-T-cytotoxic memory cell testing has been developed to reportedly determine the likelihood of acute cellular rejection (ACR) by measuring the immune response of recipient lymphocytes to donor or donor-like cells. This testing is designed for determining rejection risk in renal transplants (eg, Pleximark Tx).
• Breath Testing
  • Breath methylated alkane contour (BMAC) (eg, Heartsbreath) is a test that is purportedly indicated for use as an aid in the diagnosis of grade 3 heart transplant rejection an individual who have received a heart transplant within the preceding year. It is intended to be used as an adjunct to, and not as a substitute for an endomyocardial biopsy. The use of the test is limited to individuals who have had an endomyocardial biopsy within the previous month.
• Combined Gene Expression Profiling and Donor-Derived Cell-Free (dd-cfDNA) tests
  • These tests are designed to reportedly provide a broad assessment of immune quiescence (inactivity) and graft injury by combining a gene expression profiling test and a dd-cfDNA test (eg, AlloMap and AlloSure Heart [HeartCare], TruGraf and Viracor TRAC Kidney [OmniGraf]).

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dd-cfDNA

• Biomarker blood tests purportedly determine allograft injury by measuring DNA fragments that are supposedly released into the bloodstream from the injured donor allograft cells. The goal of these tests is to predict active rejection using these measurements. An increase in the percentage of donor-derived cell-free DNA (dd-CF DNA) in the blood indicates injury to the transplanted (ie, donor) organ that may be caused by ACR or AMR, as well as other forms of injury. These tests include, but may not be limited to:
  • AlloSure Heart
  • AlloSure Kidney
  • AlloSure Lung
  • Prospera Heart
  • Prospera Kidney with Quantification
  • Viracor TRAC (heart, kidney, liver and lung)

Urine-Based Tests for Allograft Rejection

• Several urine-based tests have been proposed utilizing various biomarkers to aid in the diagnosis of acute rejection in kidney transplant recipients.

Purportedly, the tests measure urine mRNA, urine proteins and/or urine proteomics. Some tests measure several biomarkers (eg, QiSant [also known as QSant]) to reportedly determine acute kidney transplant rejection. The biomarkers include, but may not be limited to, cfDNA, methylated cfDNA, clusterin, CXCL10, creatinine and total protein, which are integrated into an algorithm to supposedly determine kidney risk rejection scores.

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 \

who are greater than 14 days post-transplant.

• Prospera Lung
• For ongoing surveillance in lieu of biopsy to detect lung allograft injury and rejection.

The use of the criteria in this Medicare Advantage Medical Coverage Policy provides clinical benefits highly likely to outweigh any clinical harms. 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

The following gene expression profiling for transplant rejection test will not be considered medically reasonable and necessary:

• AlloMap Kidney
• Clarava
• Heartsbreath - Please refer to the above Medicare guidance
• KidneyCare
• kSORT
• MMDx Heart
• MMDx Kidney
• MMDx Lung
• nCounter Organ Transplant Panel
• OmniGraf
• Pleximark Tx
• Prospera Heart
• TruGraf Liver
• Tutivia
• Viracor TRAC Heart
• Viracor TRAC Liver
• Viracor TRAC Lung

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• Test: AlloMap
• Contraindications/Limitations:
• Less than 30 days after a blood transfusion that contains white blood cells (leukocyte-depleted red blood cell transfusion is acceptable); AND
• Corticosteroid dosage >20 mg/day: systemic corticosteroid dosage of >20 mg/day of prednisone or equivalent may result in a decreased AlloMap score; AND
• 21 days following rejection therapy with steroids: AlloMap performance characteristics have not been established for individuals who have received rejection therapy in the 21 days prior to testing
• Test: AlloSure Heart
• Contraindications/Limitations:
• Recipients of multiple transplanted organs originated from the same donor; AND
• Recipients of a bone marrow transplant; AND
• Recipients who are pregnant; AND
• Less than 24 hours following an endomyocardial biopsy
• Test: HeartCare
• Limitations:
• Until definitive studies are completed, HeartCare should not be performed on individuals within 24 hours following an endomyocardial biopsy
• Test: AlloSure Kidney
• Contraindications/Limitations:
• Recipients of transplanted organs other than kidney; AND
• Recipients of a transplant from a monozygotic (identical) twin; AND
• Recipients of a bone marrow transplant; AND
• Recipients who are pregnant; AND
• Recipients who are less than 14 days post-transplant
• Test: AlloSure Lung
• Contraindications/Limitations:
• Recipients of transplanted multi organs

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• Test Contraindications/Limitations:
• Recipients of a transplant from a monozygotic (identical) twin
• Recipients of a bone marrow / hematopoietic transplant
• Recipients who are pregnant
• Limitations:
• Following blood transfusion that contains white blood cells for 30 days (washedor leukocyte-depleted RBCs are acceptable).
• histomorphology. All AlloSure Lung results must be considered in the context of an individual’s overall clinical presentation, including other diagnostic findings, history, and examination of the individual.
• There may be differences both within and between individuals in biological variability of baseline values of dd- cfDNA.
• Damage to the graft caused by invasive procedures such as trans- bronchial lung biopsy may cause a short-term elevation of dd-cfDNA.

Until definitive studies are completed, AlloSure Lung should not be performed on individuals within 24 hours following a trans-bronchial lung biopsy.