Proposed LCD - Molecular Pathology Procedures (DL35000)

CMS National Coverage PolicyN/ACoverage Indications, Limitations, and/or Medical NecessityMolecular pathology procedures have broad clinical and research applications. The following examples of applications may not be relevant to a Medicare beneficiary or may not meet a Medicare benefit category and/or reasonable and necessary threshold for coverage. Such examples include Genetic Testing and Genetic Counseling (when applicable) for: Disease Risk, Carrier Screening, Hereditary Cancer Syndromes, Gene Expression Profiling for certain cancers, Prenatal Diagnostic testing, Diagnosis and Monitoring Non-Cancer Indications, and Several Pharmacogenomic applications.This Local Coverage Determination (LCD) addresses the circumstances under which the item or service may be reasonable and necessary. For laboratory services, a service may be reasonable and necessary if the service is safe and effective; and appropriate, including the duration and frequency that is considered appropriate for the item or service, in terms of whether it is furnished in accordance with accepted standards of medical practice for the diagnosis of the patient's condition; furnished in a setting appropriate to the patient's medical needs and condition; ordered and furnished by qualified personnel; one that meets, but does not exceed, the patient's medical need; and is at least as beneficial as an existing and available medically appropriate alternative.Many applications of the molecular pathology procedures are not covered services given lack of benefit category (e.g., preventive service or screening for a genetic abnormality in the absence of a suspicion of disease) and/or failure to the reasonable and necessary threshold for coverage (e.g., based on quality of clinical evidence and strength of recommendation or when the results would not reasonably be used in the management of a beneficiary). Furthermore, payment of claims in the past (based on stacking codes) or in the future (based on the new code series) is not a statement of coverage since the service may not have been audited for compliance with program requirements and documentation supporting the reasonable and necessary testing for the beneficiary. Certain molecular pathology procedures may be subject to prepayment medical review (records requested) and paid claims must be supportable, if selected, for post payment audit by the MAC or other contractors. Molecular pathology tests for diseases or conditions that manifest severe signs or symptoms in newborns and in early childhood or that result in early death (e.g., Canavan disease) could be subject to automatic denials since these tests are not usually relevant to a Medicare beneficiary.This LCD gives general guidance to the medically reasonable and necessary applications of the Molecular Pathology Procedures and Genomic Sequencing Procedures, described in Current Procedural Terminology (CPT).Coding guidance is provided inMolecular Pathology Procedures Article A56199, attached below.Indications:Molecular pathology procedures (Tier1 and Tier 2) may be eligible for coverage whenALLof the following criteria are met:Alternative laboratory or clinical tests to definitively diagnose the disorder/identify the condition are unavailable or results are clearly equivocal; ANDAvailability of a clinically valid test, based on published peer reviewed medical literature; ANDTesting assay(s) are Food and Drug Administration (FDA) approved/cleared or if LDT (lab developed test) or LDT protocol or FDA modified test(s) the laboratory documentation should support assay(s) of analytical validity and clinical utility; ANDResults of the testing must directly impact treatment or management of the Medicare beneficiary; ANDFor testing panels, including but not limited to, multiple genes or multiple conditions, and in cases where a tiered approach/method is clinically available, testing would be covered ONLY for the number of genes or test that are reasonable and necessary to obtain necessary information for therapeutic decision making; ANDIndividual has not previously received genetic testing for the disease/condition. (In general, diagnostic genetic testing for a disease should be performed once in a lifetime.) Exceptions include clinical scenarios whereby repeat testing of somatically-acquired mutations (for example, pre- and post- therapy) may be required to inform appropriate therapeutic decision-making.Limitations:Any procedures required prior to cell lysisshould be reported separately and utilization must be clearly supported based on the application and clinical utility. Such claims may be subject to prepayment medical review.The medically necessary interpretation and report of a molecular pathology test, written by a pathologist, which is above and beyond the report of standard laboratory results may not be reported by Non- physician practitioners (e.g., PhD, scientists etc.); only physicians are eligible to reportthis service.Testing for quality assurance component of the service is not separately billable.Indications and Limitations of CoverageABL1(ABL proto-oncogene 1, non-receptor tyrosine kinase) (eg, acquired imatinib tyrosine kinase inhibitor resistance), gene analysis, variants in the kinase domain is considered medically necessary in patients with acute lymphoblasic leukemia (ALL) and chronic myeloid leukemia (CML) to guide therapeutic decision making.ATP7Bis considered medically necessary in patients with symptoms of Wilsons disease to guide therapeutic decision making.BCR/ABLis indicated in patients with suspected CML with either persistent, unexplained leukocytosis or thrombocytosis. BCR/ABL is considered medically necessary in the evaluation of individuals with chronic myelogenous leukemia or BCR-ABL positive acute lymphoblastic leukemia to evaluate treated individuals who manifest suboptimal response to initial tyrosine kinase inhibitor therapy or loss of response to tyrosine kinase inhibitor therapy.BLM(Bloom syndrome, RecQ helicase-like)(e.g. Bloom syndrome) gene analysis, 2281 del6ins7 variant is considered medically necessary for a beneficiary who may have Bloom syndrome to confirm diagnosis and guide medical decision-making.BRAFgene analysis is considered medically necessary for patients who have malignant melanoma, non-small cell lung cancer, hairy cell leukemia, or metastatic colorectal cancer when needed to determine if a Medicare covered therapy is a reasonable option given the individual's specific clinical presentation.BRCA1 and BRCA2genetic testing is considered medically necessary for a beneficiary with a current diagnosis or a personal history of a cancer associated with the BRCA mutation who meets one or more of the criteria found in the most recent version of the NCCN guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian or other evidence based guideline addressing genetic testing, and the results will be used to benefit the individual tested in terms of potential to guide therapeutic decision making.Cardiology (heart transplant), mRNA, gene expression profiling by real-time quantitative PCR of 20 genes (11 content and 9 housekeeping), utilizing subtraction of peripheral blood, algorithm reported as rejection risk score is considered medically necessary for heart transplant patients to guide therapeutic decision-making.CEBPA(CCAAT/enhancer binding protein [C/EBP], alpha) (eg, acute myeloid leukemia), full gene sequence is considered medically necessary in patients with acute myelogenous leukemia (AML) to guide therapeutic decision making.CALR(calreticulin) (eg, myeloproliferative disorders), gene analysis, common variants in exon 9 is considered medically necessary in the initial diagnostic work-up of BCR-ABL negative, JAK2-negative adults with clinical, laboratory, or pathological findings suggesting polycythemia vera (PV), essential thrombocythemia (ET) or primary myelofibrosis (PMF).CCND1/IGH(BCL1/IgH, t)(eg, mantle cell lymphoma) translocation analysis, major breakpoint, qualitative and quantitative, if performed is considered medical necessary for patients who have non- Hodgkins lymphoma to guide therapeutic decision-making.CFTR(cystic fibrosis transmembrane conductance regulator) (e.g.cystic fibrosis) gene analysis, common variants (e.g. ACMG/ACOG guidelines) is considered medically necessary for a beneficiary who has or may have cystic fibrosis to guide therapeutic decision-making.Chimerism analysisto identify appropriate donors and monitor engraftment success or disease reoccurrence is considered medically necessary.CYP2C619-cytochrome P450 CYP2C6 19-cytochrome P450 Based on the FDAs Black Box warning for clopidogrel, the effectiveness of clopidogrel is dependent on its activation to an active metabolite by the cytochrome P450 (CYP) system, principally CYP2C19. CYP2C619 genotyping may be medically necessary once per lifetime to identify individuals:Who are poor metabolizers of clopidogrel, so that alternative treatment or treatment strategies can be consideredWho are poor metabolizers of clopidogrel with acute coronary syndrome or who are undergoing percutaneous coronary interventionCYP2C9(cytochrome P450, family 2, subfamily D polypeptide 9) (e.g., drug metabolism), gene analysis, is only considered medically necessary for individuals who have relapsing forms of multiple sclerosis, and require CYP2C9 genotyping for dosing in accordance with the FDA prescribing information for Mayzent. CYP2C9 testing must include the *1, *2, and *3 alleles that are necessary to safely dose the FDA-approved drug Mayzent.CYP2D6(cytochrome P450, family 2, subfamily D polypeptide 6) (e.g., drug metabolism), gene analysis, is only considered medically necessary for individuals with Huntingtons disease for whom doses of tetrabenazine greater than 50 mg per day are being considered, and for testing prior to the initiation of CerdelgaTM(eliglustat) for Gauchers disease.EGFR(epidermal growth factor receptor) (eg, non-small cell lung cancer) gene analysis, common variants (eg, exon 19 LREA deletion, L858R, T790M, G719A, G719S, L861Q) [when specified as EGFR mutation analysis testing] EGFR testing is considered medically necessary as a technique to predict treatment response for individuals with non-small cell lung cancer undergoing treatment with EGFR tyrosine kinase inhibitor (TKI) therapy (for example, erlotinib [Tarceva ], gefitinib [Iressa ], or afatinib [Gilotrif ]).F2gene (prothrombin coagulation factor II) andF5gene (coagulation factor V) The F2 and F5 genetic tests are not considered to be clinically efficacious; therefore, testing is not medically necessary.FLT3is considered medically necessary in patients with acute myeloid leukemia (AML) to guide therapeutic decision making.Gene Testing for Warfarin ResponsePharmacogenomic Testing for Warfarin Response, gene testing onCYP2C9 and/or VKORC1see NCD 90.1 for coverage information.HFE(hemochromatosis)(hereditary hemochrosis) gene analysis, common variants (e.g. C282Y, H63D) is considered medically necessary in patients with iron overload of uncertain etiology (e.g. when the test is used to avoid liver biopsy in someone when the ferritin and the transferrin saturation are elevated greater than 45%). The genotyping of patients with iron overload of uncertain etiology is allowed only once per lifetime.HLAClass I or II typing is considered medically necessary when one of the following indications is met:Transplantation:Standard of care determination of HLA matching for solid organ transplant (donor/recipient).  Solid organ transplant registries include both serological HLA testing (e.g., crossmatch) and genomic molecular DNA typing. Family members, or unrelated living donors or cadaveric donors who donate bone marrow or a solid organ are HLA tested pre-transplant to determine compatibility with the potential recipients.Standard of care determination of HLA matching for solid organ transplant (donor/recipient).  Solid organ transplant registries include both serological HLA testing (e.g., crossmatch) and genomic molecular DNA typing. Family members, or unrelated living donors or cadaveric donors who donate bone marrow or a solid organ are HLA tested pre-transplant to determine compatibility with the potential recipients.Standard of care identification of determination of HLA matching for hematopoietic stem cell/bone marrow transplantation -allele-level typing will provide clinical guidance for the HLA-A,B,C Class I and DRB1, DQB1,DPB1, and DQA1 Class II loci in the average transplant program because it is well established that mismatches at certain HLA loci between donor-recipients are closely linked to the risk of graft versus host disease. Potential marrow donors may enroll with a national registry such as the United States National Marrow Donor Program or the Canadian Blood Services registry.Disease Association:Standard of care testing to diagnose certain HLA related diseases/conditions when the testing is supported by the clinical literature and is informative for the direct management of a patient bearing a certain allele(s). It is not expected that more than one test would be required in a given beneficiarys lifetime. Possible covered indications when standard laboratory testing (tissue typing) not adequate:HLA-B*27 for the diagnosis of certain cases of symptomatic patients with presumed ankylosing spondylitis or related inflammatory disease. HLA-B*27 is covered for ankylosing spondylitis in cases where other methods of diagnosis would not be appropriate or have yielded inconclusive results (NCD 190.1).In the work-up of certain patients with an unclear diagnosis of celiac disease and gluten hypersensitivity usually related to ambiguous standard laboratory results and/or inconsistent biopsy results (e.g., HLA-DQ2 by HLA-DQB1*02 and of DQ8 by HLA-DQB1*0302).Pharmacogenetics:Standard of care testing to diagnose certain HLA related drug hypersensitivity reactions when the testing is supported by the clinical literature and is informative for the direct management of a patient bearing a certain allele(s) associated to fatal skin drug reactions (Stevens-Johnson syndrome and toxic epidermal necrolysis). It is not expected that more than one test would be required in a given beneficiarys lifetime. Possible covered indications: