Response to Comments for MolDX: Genetic Testing for BCR-ABL Negative
Myeloproliferative Disease

  1. **Step-wise Testing**  
  
 **Comment:** A commenter indicated he had serious concern about stepwise
molecular testing for BCR-ABL negative myeloproliferative disease (MPD). He
noted the following reasons for MPD:  

    * Heterogeneity at presentation;  

    * Patients may present with smoldering rising blood counts   

    * Some patients with life-threateningly high cell counts; need to diagnose quicly to prevent permanent debilitation due to infarct, sepsis, or bleeding, or death;   

    * Testing only on fresh diagnostic material, not FFPE or cryopreserved tissues  

    * Sequential testing add turn-around time  

    * Differential dx includes, besides myeloproliferative disease, myelodysplasia, CMML, CML, AML, ALL, idiopathic aplastic anemia, hairy cell leukemia, lymphoma, etc.   

    * When counts are life-threatening or diagnosis is not completely obvious, initial testing is almost always urgent or emergent bone marrow aspiration and biopsy.   
  
**Comment:** A commenter writes BCR/ABL and JAK2 should be ordered at the
same time rather than JAK2 as a reflex test in patients with suspected PV, ET
and PMF. These diseases are by definition BCR/ABL negative (thus requiring
that test) and very often JAK2 positive. If they are suspected it does not
make sense to delay testing with JAK2 which is critical testing for diagnosis.
In other words you know/expect BCR/ABL to be negative so why wait before the
next step. We believe that the sequence should read if PV is suspected and
JAK2 is negative then reflex to exon 12 testing (and consider reflex to
MPR/CALR if exon 12 is negative). If ET or PMF are suspected and JAK2 is
negative should reflex first to MPL/CALR and only reflex to exon 12 if those
are negative.  
  
**Comment:** Numerous commenters indicate that a tiered reflexive approach is
often neither the most clinically appropriate nor the most economical method
of testing. They note the following:  

    * Many labs with next generations (NGS) or non-NGS multi-gene testing methods can test for all five of the genetic variants for this disease in a single assay that is more rapid and less expensive than performing five sequential single-gene assays;   

    * Other genes are often included in multi-gene myeloproliferative panels that are not included in this policy such as CSF3R, which is virtually pathognomonic for atypical chronic myeloid leukemia or chronic neutrophilic leukemia.   

    * A stepped approach is not optimal because many of these diseases have effective FDA-approved therapies that need to be initiated immediately, citing 2-3 week turn around for sequential testing vs 3-10 days for simultaneous multi-gene or NGS testing  

    * Mutations in CBL, TET2, SRSF2 or ASXL1 would favor a diagnosis of CMML  

    * Considerable clinical and morphologic overlap exists between various MPNs and some of the MDS/MPNs so a tiered approach is often not applicable.  

    * JAK2 is commonly mutated in other myeloid neoplasm (non-MPNs), as well as, age-related clonal hematopoiesis or indeterminate potential.  
  
 **Response:** This Medicare contractor appreciates the above important
comments, and has changed the policy to include coverage for multi-gene panel
or NGS testing. In addition, this contractor agrees that concurrent BCR-ABL
and JAK2 testing is medically reasonable and necessary if the clinician is
suspicious of a myeloproliferative disease when sequential testing is
performed.  
  

  2. **ICD-9 vs ICD-10 Coding**  
  
 **Comment:** ICD-9 had most myeloproliferative disorders lumped under
myelodysplasia. ICD-10 splits them into 2 categories, but sadly clinical
overlap exists and labeling one way or the other may be clinically very
arbitrary. Many clinicians code patients on the disease they have the highest
suspicion of rather than just coding for the abnormal cell counts. ICD-10,
with its specificity for cause of abnormal blood counts and EHR records that
force certain codes to be used, may be more problematic.  
  
 **Response:** Agree.  
  

  3. **Repeat Testing of Negative Diagnostic Markers**  
  
 **Comment:** An LCD must be written with much forethought and concern for not
missing caveats of specific clinical circumstances, and should not create an
access to care issue for patients with rare diseases or rare genetic
abnormalities. Ideally, a lab with initial diagnostic testing should not allow
repeat testing if negative initially. However, some patients with emergency
complications may not be facile giving good information about prior testing
under emergency circumstances. This is also complicated when a patient
presents to a new health care system, and as a result of the very primitive
interoperability of electronic health records.  
  
 **Response:** Policies are designed for the usual circumstances or norm. The
appeals process is designed to accommodate the unusual or rare situations that
fall outside of the norm, with supporting documentation in the patients
medical record.  
  

  4. **Addition of CPT Codes**  
  
 **Comment:** The commenter writes: If BCR-ABL testing and all of the other
single genes are to be covered when performed as part of these multi-gene
panels, we recommend that 81401, 81405, 81406, 81445, 81450 and 81455 be
covered to allow appropriate (lower cost) payment.  
  
 **Response:** A panel by definition has a single unit of service (UOS).
Regardless of whether a panel has 2 or 10 or 100 component parts, the UOS is
1, not the number of component parts. Consequently, a molecular panel must be
assigned 81479, 81445, 81450 or 81455, as appropriate to the descriptor.
Reimbursement of multi-gene panels and NGS does not consist of the cumulative
reimbursement of individual Tier1 or 2 CPT codes.  
  
Individual CPT Tier 1 and Tier 2 codes can only be submitted on claims when
the testing is performed sequentially, and NOT a component in a panel.  
  

  5. **Addition of ICD-10 Codes**  
  
 **Comment:** Twenty-two additional ICD-10 codes were requested to be added to
the policy.  
  
**Response:** Agree with the ICD-10 codes which have been added to the policy.  
  

  6. **CALR vs MPL/CALR Testing**  
  
 **Comment:** A commenter writes that CALR is far more useful than MPL/CALR,
we recommend that this message be made apparent in the policy. The commenter
notes appreciation for CALR coverage, but posits that it should not require a
negative JAK2 exon 12 result first.  
  
**Response:** The policy reflects the usefulness of CALR over MPL. However,
the policy does not require a negative JAK2 exon 12 result prior to CALR
coverage, rather it requires a negative JAK2V617F mutation.