Coverage Policy Manual - Arkansas Blue Cross and Blue Shield

Coverage Policy Manual

Policy #:

2022034

Category:

Pharmacy

Initiated:

August 2022

Last Review:

July 2025

Allogeneic processed thymus tissue-agdc (e.g., Rethymic)

Description:

The policy applies to the following medication: Allogeneic Processed Thymus Tissue-agdc (e.g., Rethymic).

Policy/
Coverage:

Prior Approval is required for Allogeneic processed thymus tissue–agdc (e.g., Rethymic)

The initial use of this drug requires documentation of direct physician (MD/OD) involvement in the ordering and evaluation as well as a signature in the medical records submitted for prior approval.

STANDARD REVIEW FOR DURATION OF TREATMENT COURSE OR 12 MONTHS (whichever comes first). Approval timeframes may differ for members/participants of Self-Insured plans.

Effective February 26, 2026

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

Allogeneic Processed Thymus Tissue-agdc (e.g., Rethymic) meets member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes or for members with contracts without Primary Coverage Criteria, is considered Medically Necessary and is covered when the following criteria are met:

Standard Review:

Member receives a “recommended” determination from InterQual criteria review for Allogeneic Processed Thymus Tissue-agdc (e.g., Rethymic) based on diagnosis and requested product. Click the following link to view the InterQual® criteria: https://prod.ds.interqual.com/service/connect/transparency?tid=27b0a724-ca06-4b22-846b-598b8dae52fc

Does Not Meet Primary Coverage Criteria Or Is Not Covered For Contracts Without Primary Coverage Criteria

Allogeneic Processed Thymus Tissue-agdc (e.g., Rethymic) does not meet member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes and is not covered for any indication or circumstance not described above.

For contracts without Primary Coverage Criteria, Allogeneic Processed Thymus Tissue-agdc (e.g., Rethymic) is considered not Medically Necessary and is not covered or is investigational for any indication or circumstance not described above. Not Medically Necessary or Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Please refer to a separate policy on Maximum Dosage and Frequency (policy #2025031) for pharmacologic/biologic medications.

Effective July 2025 to February 25, 2026

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

The implantation of allogeneic processed thymus tissue–agdc (e.g., Rethymic) as a one-time single administration meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for individuals with congenital athymia when ALL the following criteria are met:

For FDA labeled indications, allogeneic processed thymus tissue–agdc (e.g., Rethymic) must be dosed in accordance with the indication specific recommended dose per FDA label unless otherwise specified in the dosage and administration section.

1. Individual is 18 years of age or older; AND

2. Allogeneic processed thymus tissue–agdc (e.g., Rethymic) has been ordered under the supervision of a pediatric immunologist or other specialist with expertise in the management of congenital athymia; AND

3. The individual has a confirmed diagnosis of congenital athymia (laboratory and/or medical record documentation of the flow cytometry and genetic testing results confirming the diagnosis must be submitted.):

a. Flow cytometry must show fewer than 50 naïve T cells/cubic millimeters (CD45RA+, CD62L+) in the peripheral blood or less than 5% of total T cells being naïve in phenotype; AND

4. The diagnosis of severe combined immunodeficiency (SCID) has been ruled out (i.e., no SCID-causing genetic defects identified); AND

5. Individual has been, or will be, screened for anti-HLA antibodies prior to receiving allogeneic processed thymus tissue–agdc (e.g., Rethymic) and individuals testing positive for anti-HLA antibodies should receive allogeneic processed thymus tissue-agdc (e.g., Rethymic) from a donor who does not express those HLA alleles; AND

6. Individual will have HLA matching if they have received prior hematopoietic cell transplantation (HCT) or solid organ transplant. To minimize risk of graft-versus-host-disease, confirm HLA matching of allogeneic processed thymus tissue–agdc (e.g., Rethymic) to recipient alleles that were not expressed in the HCT donor; AND

7. Implantation of allogeneic processed thymus tissue–agdc (e.g., Rethymic) will be done by a qualified surgical team in a single surgical session at a qualified hospital; AND

8. Individual has not previously received thymus tissue implantation for the treatment of congenital athymia in their lifetime.

Dosing and Administration

Dosing per FDA Guidelines unless otherwise specified below.

The recommended dose of allogeneic processed thymus tissue–agdc implantation is a single, one-time dose, up to 22,000 square millimeters of allogeneic processed thymus tissue-agdc/square meters recipient body surface area (BSA), not to exceed 42 slices, (as calculated and supplied by the manufacturer). Implantation will not exceed this dosage and will be rendered by a qualified surgical team in a single surgical session.

Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

Allogeneic processed thymus tissue–agdc (e.g., Rethymic) for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.

For individuals with contracts without primary coverage criteria, allogeneic processed thymus tissue–agdc (e.g., Rethymic) for any indication or circumstance not described above are considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Effective August 22, 2022 to June 2025

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

The implantation of allogeneic processed thymus tissue–agdc (e.g., Rethymic) as a one-time single administration meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for individuals with congenital athymia when ALL the following criteria are met:

1. The individual is <18 years old; AND

2. Has been ordered under the supervision of a pediatric immunologist or other specialist with expertise in the management of congenital athymia; AND

3. The individual has a confirmed diagnosis of congenital athymia (laboratory and/or medical record documentation of the flow cytometry and genetic testing results confirming the diagnosis must be submitted.)

a. Flow cytometry must show fewer than 50 naïve T cells/cubic millimeters (CD45RA+, CD62L+) in the peripheral blood or less than 5% of total T cells being naïve in phenotype; AND

4. The diagnosis of severe combined immunodeficiency (SCID) has been ruled out (i.e., no SCID-causing genetic defects identified); AND

5. The individual has been, or will be, screened for anti-HLA antibodies prior to receiving Rethymic and individuals testing positive for anti-HLA antibodies should receive allogeneic processed thymus tissue-agdc (e.g., Rethymic) from a donor who does not express those HLA alleles; AND

6. The individual will have HLA matching if they have received prior hematopoietic cell transplantation (HCT) or solid organ transplant. To minimize risk of graft-versus-host-disease, confirm HLA matching of Rethymic to recipient alleles that were not expressed in the HCT donor; AND

7. Implantation of allogeneic processed thymus tissue–agdc (e.g., Rethymic) will be done by a qualified surgical team in a single surgical session at a qualified hospital; AND

8. The individual has not previously received thymus tissue implantation for the treatment of congenital athymia in their lifetime; AND

9. Must be dosed in accordance with the FDA label.

Dosing and Administration

Dosing per FDA Guidelines

Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

For individuals with contracts without primary coverage criteria, allogeneic processed thymus tissue–agdc (e.g., Rethymic) for any indication or circumstance not decirbed above are considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Rationale:

Transplantation of fetal thymus tissue to correct cDGS was discovered more than 50 years ago, but it was met with limited success. Use of postnatal thymus tissue obtained from infant donors undergoing cardiac surgery for congenital heart disease started at Duke University in 1993; removal of thymus tissue is necessary for cardiac surgery in these infants. The removed thymus requires culturing for 13-20 days before transplantation to deplete thymocytes while preserving the thymic stroma. This process has been shown to be consistent between slices of the same thymus and between different thymus cultures. The stromal cells retain over 90% estimated viability and the thymus donor is not tissue type-matched with the recipient.

The efficacy of Rethymic was evaluated in 10 prospective, single-center, open-label studies that enrolled a total of 105 patients, including 95 patients in the primary efficacy analysis. The median (range) age at the time of treatment was 9 months (1-36). The diagnosis of congenital athymia was based on flow cytometry documenting fewer than 50 naïve T cells/mm3 (CD45RA+, CD62L+) in the peripheral blood or less than 5% of total T cells being naïve in phenotype in 91/95 patients (range 0-98 naïve T cells/mm3). In addition to congenital athymia, patients also had complete DiGeorge syndrome (cDGS) if they also met at least one of the following criteria: congenital heart defect, hypoparathyroidism, 22q11 hemizygosity, 10p13 hemizygosity, CHARGE (coloboma, heart defect, choanal atresia, growth and development retardation, genital hypoplasia, ear defects including deafness) syndrome, or CHD7 mutation. Across the efficacy population, 93 patients (98%) were diagnosed with cDGS. Patients who did not have congenital athymia (e.g., SCID) and patients with prior transplants, including thymus and HCT, were excluded from the efficacy analysis population. Additionally, patients with heart surgery anticipated within 4 weeks prior to, or 3 months after, the planned Rethymic treatment date, patients with HIV infection, and patients who were not considered good surgical candidates were excluded from study participation.

Patients in the efficacy population received Rethymic in a single surgical procedure at a dose of 4,900 to 24,000 mm2 of Rethymic per recipient body surface area (BSA) in m2. Patients were assigned to receive immunosuppressive therapy prior to and/or after treatment according to their disease phenotype and pre-Rethymic phytohemagglutinin (PHA) response. No patients were retreated with Rethymic.

The Kaplan-Meier estimated survival rates were 77% (95% CI [0.670, 0.841]) at 1 year and 76% (95% CI [0.658, 0.832]) at 2 years. For patients who were alive at 1 year after treatment with Rethymic, the survival rate was 94% at a median follow-up of 10.7 years.

Of the 105 patients that have received cultured thymus tissue (CCT), 76 are still alive. Of the 29 patients who died, 23 passed away within 12 months of the implantation. Of the 6 patients who died more than 1 year post implantation, the deaths were considered unrelated to study treatment (2 patients died due to respiratory failure and 1 patient each died following cardiopulmonary arrest, intracranial hemorrhage, infection, and unknown cause).

2023 Update

Annual policy review completed with a literature search using the MEDLINE database through August 2023. No new literature was identified that would prompt a change in the coverage statement.

2024 Update

Annual policy review completed with a literature search using the MEDLINE database through August 2024. No new literature was identified that would prompt a change in the coverage statement.

2025 Update

Annual policy review completed with a literature search using the MEDLINE database through July 2025. No new literature was identified that would prompt a change in the coverage statement.

CPT/HCPCS:

References:

Markert ML, Gupton SE, McCarthy EA.(2022) Experience with cultured thymus tissue in 105 children. J Allergy Clin Immunol. 2022;149(2):747-757. doi:10.1016/j.jaci.2021.06.028.

Rethymic (allogeneic processed thymus tissue-agdc) New Drug Review. IPD Analytics. Updated October, 2021.

Rethymic [package insert]. Enzyvant Therapeutics, Inc. Cambridge, MA. Updated October 2021.

Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants.