MolDX: Molecular Testing for Solid Organ Allograft Rejection

Jurisdiction: J15 MAC Part B. States: Kentucky, Ohio. Type: Active LCD

DEFINITIONS For purposes of this policy the following definitions are used: AR – Acute Rejection ACR – Acute Cellular Rejection (also referred to as TCMR: T-cell mediated rejection) AMR – Antibody-Mediated Rejection AV – Analytical Validity CV – Clinical Validity cfDNA – Donor-Derived Cell-Free DNA GEP – Gene Expression Profiling SubAR - Subclinical acute rejection For-Cause – patient has clinical signs or symptoms of organ injury/rejection. Surveillance (Protocol) – patient is asymptomatic; no clinical signs or symptoms of organ injury/rejection. This Medicare contractor will provide limited coverage for molecular diagnostic tests used in the evaluation and management of patients who have undergone solid organ transplantation. These tests can inform decision making along with standard clinical assessments in their evaluation of organ injury for active rejection (AR). These tests may be ordered by qualified physicians or providers operating within their scope of practice considering the diagnosis of AR, helping to rule in or out this condition and when assessing the need for or results of a diagnostic biopsy. They should be considered along with other clinical evaluations and results and may be particularly useful in patients with significant contraindications to invasive procedures. Molecular diagnostic tests that assess a transplanted allograft for rejection status are covered when ALL of the following criteria are met: The test must provide information about at least one of the two following clinical status determinations: AR status Cellular or Antibody-mediated rejection (ACR or AMR) status The intended use of the test must be to inform clinical decision making as per the following: To assist in the evaluation of adequacy of immunosuppression or response to treatment, wherein a non-invasive or minimally invasive test can be used in lieu of a tissue biopsy, OR As a rule-out test for AR in validated populations of patients with clinical suspicion of rejection with a non-invasive or minimally invasive test to make a clinical decision regarding obtaining a biopsy, OR For further evaluation of allograft status for the probability of allograft rejection after a physician-assessed pretest review of clinical and biological factors concerning for risk of rejection, OR To assess rejection status in patients that have received a biopsy, but the biopsy results are inconclusive, unexpected given the patient’s clinico-laboratory presentation, or limited by insufficient material, OR To assess for subclinical rejection of an allograft (i.e., surveillance testing), according to a clinically validated cadence (in peer-reviewed published evidence or established national consensus guidelines) utilizing the minimum number of test timepoints that have demonstrated clinical utility appropriate for the specific transplant type. At this time, the current evidence supports a maximum number of surveillance timepoints for evaluation in the first-year post-transplantation as follows: Kidney (4), Heart (12), and Lung (12). After the first year, surveillance timepoints may continue at a decreased frequency of 2 per year. The test demonstrates analytical validity (AV), including an analytical and clinical validation for any given measured analytes, and has demonstrated equivalence or superiority for sensitivity or specificity (depending on intended use) of detecting allograft rejection to other already-accepted tests for the same intended use measuring the same or directly comparable analytes under this policy. Clinical validity (CV) of any analytes (or expression profiles) measured must be established through a study published in the peer-reviewed literature for the intended use of the test in the intended population. The degree of validity must be similar or superior to established and covered tests under this policy (see associated coverage Articles). If conducted with concordance to tissue histologic evaluation, the appropriate Banff Classification for renal allografts or other accepted criteria (if existing) must be used. The test is being used in a patient who is part of the population (disease and intended use) in which the test was analytically validated and has demonstrated CV. For a given patient encounter, only one molecular test for assessing allograft status may be performed. A test may include more than one assay; however, multianalyte and combination tests must demonstrate superiority and additive benefit when compared to respective single analytes or components. For minimally or non-invasive tests, the benefit to risk profile of the molecular test is considered by the ordering clinician to be more favorable than the benefit to risk profile of a tissue biopsy, or a tissue biopsy cannot be obtained, when the test and biopsy provide similar information. For example, this may be the case if a biopsy is considered medically contraindicated in a patient. The test successfully completes a MolDX Technical Assessment that will ensure that AV, CV, and clinical utility criteria set in this policy are met to establish the test as reasonable and necessary. A test and biopsy cannot be performed simultaneously. However, in very high-risk patients with overt signs and symptoms of rejection, a molecular test and biopsy may be performed together in urgent situations ONLY when the information derived from the test is complementary to the biopsy, established to meet CV requirements outlined above for that information, and demonstrated to improve outcomes in patients when performed along with biopsies. We expect these situations to be extremely rare. Covered tests with AV that is significantly below similar services may have coverage rescinded.