Sunflower Health Plan Allogenic Processed Thymus Tissue-agdc (Rethymic) Form

Allogenic processed thymus tissue-agdc (Rethymic®) is a regenerative tissue-based therapy. FDA Approved Indication(s) Rethymic is indicated for immune reconstitution in pediatric patients with congenital athymia. Limitation(s) of use: Rethymic is not indicated for the treatment of patients with severe combined immunodeficiency (SCID). Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria. It is the policy of health plans affiliated with Centene Corporation® that Rethymic is medically necessary when the following criteria are met: I. Initial Approval Criteria A. Congenital Athymia (must meet all): 1. Diagnosis of congenital athymia; 2. Diagnosis is confirmed by CD3+ CD4+ CD45RA+ CD62L+ T-cell count < 50/mm3 or < 5% of the total T-cell count based on flow cytometry; 3. One of the following (a or b): a. Absence of genetic defects associated with SCID (see Appendix E); b. At least one of the following to define complete DiGeorge syndrome (cDGS): congenital heart defect, hypoparathyroidism/hypocalcemia, 22q11 hemizygosity, 10p13 hemizygosity, CHARGE syndrome (see Appendix D), or CDXH7 mutation; 4. Prescribed by or in consultation with a pediatric immunologist; 5. Age ≤ 18 years; 6. Member does not have preexisting CMV infection (e.g., > 500 copies/mL in the blood by PCR on two consecutive assays); 7. Documentation of anti-human leukocyte antigen (HLA) antibody screening prior to treatment; 8. If positive for anti-HLA antibodies, member must receive Rethymic from a donor who does not express HLA alleles; Page 1 of 6 CLINICAL POLICY Allogenic Processed Thymus Tissue-agdc 9. If member previously received a hematopoietic cell transplantation (HCT) or a solid organ transplant, both of the following (a and b): a. HLA matching is required; b. Member must receive Rethymic HLA matched to recipient alleles that were not expressed in the HCT donor; 10. Rethymic is prescribed in combination with immunosuppressive therapy based on disease phenotype and phytohemagglutinin (PHA) levels (see Appendix F); 11. Request meets both of the following (a and b); a. Dose does not exceed 22,000 mm2 of Rethymic /m2 recipient body surface area (up to 42 Rethymic slices); b. Request is for a one-time application only. Approval duration: 1 month (one time application only per lifetime) II. Continued Therapy A. Congenital Athymia 1. Continued therapy will not be authorized as Rethymic is indicated to be dosed one time only. Approval duration: Not applicable III. Diagnoses/Indications for which coverage is NOT authorized: A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ATG-R: anti-thymocyte globulin (rabbit) cDGS: complete DiGeorge syndrome CMV: cytomegalovirus CPM: counts per minute FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives Not applicable HCT: hematopoietic cell transplantation HLA: human leukocyte antigens MMF: mycophenylate mofetil PHA: phytohemagglutinin SCID: severe combined immunodeficiency Appendix C: Contraindications/Boxed Warnings None reported Appendix D: General Information • Congenital athymia is a rare condition characterized by the absence of a thymus at birth resulting in profound immunodeficiency and immune dysregulation. Children with congenital athymia generally do not survive beyond early childhood. • CHARGE syndrome is a disorder that affects many areas of the body. CHARGE is an abbreviation for several of the features common in the disorder: coloboma, heart defects, Page 2 of 6 CLINICAL POLICY Allogenic Processed Thymus Tissue-agdc atresia choanae (also known as choanal atresia), growth retardation, genital abnormalities, and ear abnormalities. Appendix E: SCID Defects Disease γc deficiency (X-linked SCID, CD132 deficiency JAK3 deficiency IL7Rα deficiency CD45 deficiency CD3δ deficiency CD3ε deficiency CD3ζ deficiency Coronin-1A deficiency LAT deficiency RAG deficiency DCLRE1C (Artemis) deficiency DNA PKcs deficiency Cernunnos/XLF deficiency DNA ligase IV deficiency Adenosine deaminase (ADA) deficiency AK2 defect Activated RAC2 defect Genetic Defect IL2RG JAK3 IL7R PTPRC CD3D CD3E CD3Z CORO1A LAT RAG 1, RAG 2 DCLRE1C PRKDC NHEJ1 LIG4 ADA AK2 RAC2 Appendix F: Treatment Assignment to Immunosuppression Complete DiGeorge Anomaly Phenotype Typical PHA Response < 5,000 cpm or < 20-fold response to PHA over background > 5,000 cpm and < 50,000 cpm or evidence of maternal engraftment > 50,000 cpm Typical Typical Atypical Atypical < 40,000 cpm on immunosuppression or < 75,000 cpm when not on immunosuppression > 40,000 cpm on immunosuppression or > 75,000 cpm when not on immunosuppression or evidence of maternal engraftment Page 3 of 6 Immunosuppression Used with Rethymic None ATG-R Methylprednisolone ATG-R Methylprednisolone Cyclosporine ATG-R Methylprednisolone Cyclosporine ATG-R Methylprednisolone Cyclosporine Basiliximab MMF CLINICAL POLICY Allogenic Processed Thymus Tissue-agdc V. Dosage and Administration Indication Congenital athymia Dosing Regimen 5,000 to 22,000 mm2 of Rethymic surface area per m2 of recipient BSA as a single surgical procedure Maximum Dose 22,000 mm2 of Rethymic surface area/m2 recipient BSA; up to 42 cultured Rethymic slices VI. Product Availability Slices of processed tissue with varying thickness and shape; each drug product dish contains up to 4 Rethymic slices VII.