LCD Reference Article Response To Comments Article

Response to Comments: MolDX: Blood Product Molecular Antigen Typing

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A58505
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Response to Comments: MolDX: Blood Product Molecular Antigen Typing
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Response to Comments
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12/06/2020
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The comment period for the MolDX: Erythrocyte Molecular Antigen Typing DL38331 Local Coverage Determination (LCD) began on 10/22/2019 and ended on 12/06/19. The notice period for L38331 begins on 10/22/2020 and will become effective on 12/06/2020.

The title of the LCD was revised from MolDX: Erythrocyte Molecular Antigen Typing to MolDX: Blood Product Molecular Antigen Typing. The comments below were received from the provider community.

Response To Comments

Number Comment Response
1

The following comment was submitted to CGS, Noridian, and Palmetto GBA:

Thank you for the opportunity to review and comment on the proposed coverage policy for Erythrocyte Molecular Antigen Typing. The Association for Molecular Pathology (AMP) is an international medical and professional association representing approximately 2,300 physicians, doctoral scientists, and medical technologists who perform or are involved with laboratory testing based on knowledge derived from molecular biology, genetics, and genomics. Membership includes professionals from the government, academic medicine, private and hospital-based clinical laboratories, and the in vitro diagnostics industry.

The College of American Pathologists (CAP) is the world’s largest organization of board-certified pathologists and leading provider of laboratory accreditation and proficiency testing programs. The CAP serves patients, pathologists, and the public by fostering and advocating excellence in the practice of pathology and laboratory medicine worldwide.

Members of AMP and the CAP appreciate the willingness of the contractors to offer limited coverage for molecular typing of red blood cell antigens using both FDA-approved tests and laboratory developed tests that meet the criteria outlined in the proposed policy. Given the level of evidence at this time our organizations agree with the limited coverage that is outlined in the proposed policy.

Thank you again for the opportunity to review and comment on this proposed policy.

Thank you for your comments and support of the policy.

2

Thank you for the opportunity to comment on DL38240, MolDx Erythrocyte Molecular Antigen Typing. Overall, we agree with the coverage guidance, including the description of FDA-approved/cleared tests and LDTs that meet the criteria as stated in the proposed coverage determination. We are pleased to see MolDX’s recognition of the rise in therapies that are shown to interfere with serology-based assays. We do have a few comments and suggestions, as detailed below:

Comment 1: In the “Summary of Evidence” section, there are two FDA-approved tests described. However, in the last paragraph, redundant text from the previous LCD L36074 remains. From our point-of-view, this legacy statement of coverage conflicts with the coverage guidance as it does not address the second FDA-approved test, nor LDTs. We recommend removing the following paragraph from the evidence summary as this would likely cause confusion with the stated coverage guidance.

“Medicare will cover pretransfusion molecular testing using the HEA BeadChip™ assay for the following categories of patients:

  • Long term, frequent transfusions anticipated to prevent the development of alloantibodies (e.g. sickle cell anemia, thalassemia or other reason);
  • Autoantibodies or other serologic reactivity that impedes the exclusion of clinically significant alloantibodies (e.g. autoimmune hemolytic anemia, warm autoantibodies, patient recently transfused with a positive DAT, high-titer low avidity antibodies, patients about to receive or on daratumumab therapy, other reactivity of no apparent cause);
  • Suspected antibody against an antigen for which typing sera is not available; and
  • Laboratory discrepancies on serologic typing (e.g. rare Rh D antigen variants)

Medicare does not expect molecular testing to be performed on patients undergoing surgical procedures such as bypass or other cardiac procedures, hip or knee replacements or revisions, or patients with alloantibodies identifiable by serologic testing that are not expected to require long term, frequent transfusions.”

Comment 2: In the “CPT/HCPCS Codes” section, the additional CPT-PLA code for the ID CORE XT test, as described in the “Summary of Evidence” section, is missing. If CPT codes are listed in this section, the following should be added to the Group 1 codes for completeness:

CODE: 0084U

DESCRIPTION: Red blood cell antigen typing, DNA, genotyping of 10 blood groups with phenotype prediction of 37 red blood cell antigens

Comment 3: The proposed LCD recognizes that the anti-CD47 antibodies now on the rise to treat various cancers have a proven interference with serological testing for red cell antigen identification. In the “Summary of Evidence” section, the LCD recognizes that “More recent evidence suggests that the treatment with Hu5F9-G4, and IgG4 monoclonal antibody targeting CD47 also interferes with pretransfusion testing.” However, the table under the “ICD10 Codes that Support Medical Necessity” is missing a number of diseases that have published application of anti-CD47, including:

  • Acute myeloid leukemia (AML)
  • Acute lymphoblastic leukemia (ALL)
  • Non-Hodgkin’s lymphoma (NHL)
  • Myelodysplastic Syndrome (MDS)

Anti- CD47 Application          

  • AML       Publication
      • Liu J, Wang L, Zhao F, et al. Pre-clinical development of a humanized anti-CD47 antibody with anti-cancer therapeutic potential. PLoS One 2015;10:e0137345
      • Vonderheide RH. CD47 blockade as another immune checkpoint therapy for cancer. Nat Med. 2015 Oct;21(10):1122-3. doi: 10.1038/nm.3965
      • Sallman DA, et al. The first-in-class anti-CD47 antibody Hu5F9-G4 is active and well tolerated alone or with azacitidine in AML and MDS patients: Initial phase 1b results. Journal of Clinical Oncology 2019 37:15_suppl, 7009-7009
      • Russ A, et al. Blocking "don't eat me" signal of CD47-SIRPα in hematological malignancies, an in-depth review. Blood Rev. 2018 Nov;32(6):480-489. doi: 10.1016/j.blre.2018.04.005. Epub 2018 Apr 14
  • ALL          Publication
      • Mark P. Chao, Ash A. Alizadeh, Chad Tang, et al. Therapeutic antibody targeting of CD47 eliminates human acute lymphoblastic leukemia
      • Cancer Res. 2011 Feb 15; 71(4): 1374–1384. Published online 2010 Dec 21. Doi: 10.1158/0008-5472.CAN-10-2238
  • NHL          Publication
      • Liu J, Wang L, Zhao F, et al. Pre-clinical development of a humanized anti-CD47 antibody with anti-cancer therapeutic potential. PLoS One 2015;10:e0137345.
      • Vonderheide RH. CD47 blockade as another immune checkpoint therapy for cancer. Nat Med. 2015 Oct;21(10):1122-3. doi: 10.1038/nm.3965
      • Advani R, Flinn I, Popplewell L, et al. CD47 Blockade by Hu5F9-G4 and Rituximab in Non-Hodgkin’s Lymphoma N Engl J Med 2018; 379:1711-1721
      • Advani R, et al. CD47 Blockade by Hu5F9-G4 and Rituximab in NonHodgkin’s Lymphoma. N Engl J Med 2018; 379:1711-1721
  • MDS          Publication
      • Sallman DA, et al. The first-in-class anti-CD47 antibody Hu5F9-G4 is active and well tolerated alone or with azacitidine in AML and MDS patients: Initial phase 1b results. Journal of Clinical Oncology 2019 37:15_suppl, 7009-7009
      • Russ A, et al. Blocking "don't eat me" signal of CD47-SIRPα in hematological malignancies, an in-depth review. Blood Rev. 2018 Nov;32(6):480-489. doi: 10.1016/j.blre.2018.04.005. Epub 2018 Apr 14

For your convenience, below is the list of applicable ICD-10 codes we suggest should be added to the medical necessity table.

ICD-10 CODE          DESCRIPTION

C92.6                      Acute myeloid leukemia with 11q23abnormality

C92.A                      Acute myeloid leukemia with multilineage dysplasia

C92.A1                    Acute myeloid leukemia with multilineage dysplasia, in remission

C92.A2                    Acute myeloid leukemia with multilineage dysplasia, in relapse

C92.61                    Acute myeloid leukemia with multilineage dysplasia, in relapse

C92.62                    Acute myeloid leukemia with 11q23abnormality in relapse

C92.60                    Acute myeloid leukemia with 11q23abnormality not having achieved remission

C92.A0                    Acute myeloid leukemia with multilineage dysplasia, not having achieved remission            

C85.97                    Non-Hodgkin lymphoma, unspecified, spleen

Z85.72                    Personal history of non-Hodgkin lymphoma

C85.90                    Non-Hodgkin lymphoma, unspecified, unspecified site

C85.80                    Other specified types of non-Hodgkin lymphoma, unspecified site

C85.92                    Non-Hodgkin lymphoma, unspecified, intrathoracic lymph nodes

C85.96                    Non-Hodgkin lymphoma

C85.9                      Non-Hodgkin lymphoma, unspecified

C85.99                    Non-Hodgkin lymphoma, unspecified, extranodal and solid organ sites

C85.91                    Non-Hodgkin lymphoma, unspecified, lymph nodes of head, face, and neck

C85.89                    Other specified types of non-Hodgkin lymphoma, extranodal and solid organ sites

C85.93                    Non-Hodgkin lymphoma, unspecified, intraabdominal lymph nodes

C85.98                    Non-Hodgkin lymphoma, unspecified, lymph nodes of multiple sites

C85.94                    Non-Hodgkin lymphoma, unspecified, lymph nodes of axilla and upper limb

C85.95                    Non-Hodgkin lymphoma, unspecified, lymph nodes of inguinal region and lower limb

C85                         Other specified and unspecified types of non-Hodgkin lymphoma

C91.02                    Acute lymphoblastic leukemia, in relapse

C91.01                    Acute lymphoblastic leukemia, in remission

C91.00                    Acute lymphoblastic leukemia not having achieved remission

D46                         Myelodysplastic Syndrome

D46.9                      Myelodysplastic Syndrome, unspecified

D46.C                      Myelodysplastic Syndrome with isolated del(5q) chromosomal abnormality

D46.Z                      Other Myelodysplastic Syndrome

 

Thank you for your comments and support of the policy. We have made changes and expanded the ICD 10 codes as you suggested and addressed the content.

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Associated Documents

Medicare BPM Ch 15.50.2 SAD Determinations
Medicare BPM Ch 15.50.2
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