Thursday, August 1, 2024

MolDx Issues New Draft LCD: Myeloproliferative Neoplasms if BCR ABL Negative

There's nothing wrong with the title of the new MolDx proposed LCD, but if you're outside the field it will probably be puzzling and it's notable for a "double negative."  It's DL399919, released for comment on August 1, 2024.

MolDX: Non-Next Generation Sequencing Tests for the Diagnosis of BCR-ABL Negative Myeloproliferative Neoplasms

The request was "MAC initiated."  Find the LCD here DL39919. Comment period open to 9-15-24.

It's for NON-NGS methods, because NGS methods are covered by a prior LCD (L38047).

It's for leukemias and for related conditions (myelofibrosis, polycythemia vera) that are "non classical" aka "BCR ABL" negative.   It comes with a pre-fab billing article, DA59827.  A59827 lists a number of CPT codes (e.g. 81270 JAK2) and PLA codes 0027U, 0040U both of which are single-gene analyses.

There are 18 journal articles cited.

There are 11 coverage rules, but some of them are complex with multiple subheadings or sub-subheadings.


AI CORNER

I asked Chat GPT to summarize the 11 rules and sub-rules "in plain English."  This is for curiousity only; you have to see the actual detailed rules and conditions - exactly as writtten by Palmetto - to understand the coverage.  Chat GPT writes:

Here is a simplified summary of the Medicare policy criteria for molecular testing in patients with hematopoietic diseases:

  1. Diagnostic Criteria: The patient must be evaluated for certain diseases using recognized diagnostic standards (like WHO or ICC).

  2. Initial Testing Sequence: Testing should begin with BCR-ABL assessment unless polycythemia vera (PV) is suspected.

  3. Test Sensitivity: The test must be able to detect very small genetic changes, especially in the JAK2, CALR, and MPL genes.

  4. Sequential Testing: If using single-gene tests, stop further testing once a relevant result is found unless more testing is specifically needed. Follow a sequence: Start with BCR-ABL, then JAK2, and continue if needed.

  5. Panel Testing Requirements: If using a panel of tests, it must include all necessary genes for the specific condition suspected. For example, if acute myeloid leukemia is suspected, include relevant mutations in the test panel.

  6. Further Testing: If initial tests don't find mutations but suspicion remains, a more comprehensive test like an NGS panel may be used.

  7. Clinical Validity: The test must be proven to work for its intended purpose in the relevant patient group, with supporting published studies.

  8. Appropriate Use: The test must be used correctly in the right patient group and for the correct purpose.

  9. Technical Assessment: The test must pass a technical evaluation to confirm its accuracy, clinical relevance, and usefulness.

  10. Comparison with Standards: The test must be as good as or better than existing tests in terms of accuracy and reliability.

  11. Purpose of Testing: The test should be used for diagnosis, not for checking if a disease is cured or for monitoring minimal disease levels. [/end Chat GPT]

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Comparison



Original

Chat GPT “Plain English”

ALL of the following criteria must be met:

 

1. The patient is being evaluated for a BCR-ABL-negative MPN according to national or international consensus diagnostic criteria (i.e., World Health Organization (WHO); International Consensus Classification (ICC)).

 

2. Testing follows the assessment of BCR-ABL (this is required unless the patient is only suspected of having PV).

 

3. The test is comprised of one or more highly sensitive single- or multi- gene assays (i.e. quantitative polymerase chain reaction [PCR], digital droplet PCR [ddPCR]) that can accurately detect a minimum variant allele frequency (VAF) of <1% for JAK2 (and 1-3% for CALR and MPL when they are included in the testing).

 

4. If testing is performed using single gene tests, a sequential and reflexive approach is expected. Once a positive result is obtained and the appropriate diagnosis is established, further testing should stop unless otherwise indicated and as further described below.

  • When testing for the classical BCR-ABL-negative MPNs (PV, ET, or PMF) using single gene tests, reflex testing to the next gene will be considered reasonable and necessary according to the following sequence of tests for known driver mutations:
    1. BCR-ABL negative test results, progress to ii.
      • Note: For the rare patient with high clinical suspicion of PV despite a positive BCR-ABL result, testing for a mutation in Janus Kinase 2 (JAK2) mutation may still be performed.
    2. JAK2 V617F negative test results (this includes JAK2 V617F positive at <1% VAF), progress to iii or iv.
    3. JAK2, exon 12 (required when PV is suspected)
    4. Calreticulin (CALR) and Thrombopoietin Receptor (MPL) driver mutations (required when ET or PMF is suspected)
      • NOTE: testing for CALR/MPL does NOT require a negative JAK2 exon 12, just a negative JAK2 V617F result.

 

5. If testing is performed using a panel (i.e., multiplex PCR) the panel must include at least the minimum necessary genes and gene alterations that would be reasonably expected by the test to achieve a diagnosis according to national or international consensus guidelines, given the specific MPN subtype suspected. For example:

  • Molecular testing for mutations in JAK 2 (including V617F and exon 12), CALR and MPL genes is considered medically necessary for the identification of the classical MPNs.
    1. However, if the Accelerated/blast phase of PMF is suspected at diagnosis, molecular testing should also include acute myeloid leukemia (AML)- associated mutations and would likely require the performance of a NGS panel; in this case, a panel that does not include the AML-associated mutations does not meet the minimum necessary gene requirements.
  • Additional MPN-associated genes must also be included as appropriate for the identification of other non-classical BCR-ABL-negative MPNs. For example, when CNL is suspected, testing for the colony stimulating factor 3 receptor (CSF3R) is required. Note also that testing for CNL requires the exclusion of the classical BCR-ABL-negative MPNs.

 

6. Patients with high suspicion of a BCR-ABL negative MPN who test negative by a non-NGS test for mutations in JAK2 (including the detection of JAK2 V617F at a VAF <1%), CALR, MPL and/or CSF3R may have a subsequent NGS panel performed for additional relevant mutations, as outlined in national or international consensus guidelines. The additional testing by NGS must comprise non-duplicative genetic alterations and fulfill the criteria outlined in this policy.

 

7. Clinical validity (CV) of analytes measured must be established through a study published in the peer-reviewed literature for the intended use of the test in the intended population.

 

8. The test is being used (a) in a patient who is part of the population in which the test was analytically validated and (b) according to the intended use of the test.

 

9. The test satisfactorily completes a technical assessment (TA) that will evaluate and confirm that the analytical validity (AV), clinical validity (CV), and clinical utility (CU) criteria set in this policy are met to establish the test as Reasonable and Necessary.

 

10. Tests utilizing a similar methodology or evaluating a similar molecular analyte to a test for which there is a generally accepted testing standard or for which existing coverage exists must demonstrate equivalent or superior test performance (i.e., sensitivity and/or specificity) when used for the same indication in the intended-use population.

 

11. Testing is performed for diagnosis and not as a test of cure or for monitoring minimal residual disease (MRD

 

Here is a simplified summary of the Medicare policy criteria for molecular testing in patients with hematopoietic diseases:

  1. Diagnostic Criteria: The patient must be evaluated for certain diseases using recognized diagnostic standards (like WHO or ICC).
  2. Initial Testing Sequence: Testing should begin with BCR-ABL assessment unless polycythemia vera (PV) is suspected.
  3. Test Sensitivity: The test must be able to detect very small genetic changes, especially in the JAK2, CALR, and MPL genes.
  4. Sequential Testing: If using single-gene tests, stop further testing once a relevant result is found unless more testing is specifically needed. Follow a sequence: Start with BCR-ABL, then JAK2, and continue if needed.
  5. Panel Testing Requirements: If using a panel of tests, it must include all necessary genes for the specific condition suspected. For example, if acute myeloid leukemia is suspected, include relevant mutations in the test panel.
  6. Further Testing: If initial tests don't find mutations but suspicion remains, a more comprehensive test like an NGS panel may be used.
  7. Clinical Validity: The test must be proven to work for its intended purpose in the relevant patient group, with supporting published studies.
  8. Appropriate Use: The test must be used correctly in the right patient group and for the correct purpose.
  9. Technical Assessment: The test must pass a technical evaluation to confirm its accuracy, clinical relevance, and usefulness.
  10. Comparison with Standards: The test must be as good as or better than existing tests in terms of accuracy and reliability.
  11. Purpose of Testing: The test should be used for diagnosis, not for checking if a disease is cured or for monitoring minimal disease levels.

 

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It's not written in a way that's not hard to understand.

Here's an AI summary of the body of the LCD (the literature analysis and conclusions) - here.