Last Review Date: 02/04/2025

Date of Origin:  02/04/2025

Dates Reviewed:  02/2025

1. Length of Authorization

Coverage will be provided for 1 month and may be renewed.

2. Dosing Limits

A. Max Units (per dose and over time) [HCPCS Unit]:

•  225 million MSC twice a week for 4 weeks (up to 16 total doses)

3. Initial Approval Criteria ¹

Coverage for is provided for treatment of the following conditions:

• Patient is at least 2 months of age; AND

Acute Graft-Versus-Host Disease (aGVHD) † Ф ^1-7

• Patient has steroid-refractory disease (defined as disease that shows progression within 3 days, or no improvement within 7 days of consecutive treatment with 2 mg/kg/day methylprednisolone or equivalent); AND
• Patient does not have skin-only involvement or evidence of encephalopathy or diffuse alveolar hemorrhage or other active pulmonary disease; AND
• Patient does not have a known hypersensitivity to dimethyl sulfoxide (DMSO) or porcine and bovine proteins; AND
• Patient is post-allogeneic stem cell transplant (Note: Symptoms of aGVHD typically appear before day 100)

† FDA Approved Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug

4. Renewal Criteria ^1,5

Coverage can be renewed based on the following criteria:

• Patient continues to meet the universal and other indication-specific relevant criteria identified in section III; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: severe infusion related reactions, hypersensitivity reactions, etc.; AND
  • Patient has experienced at minimum a partial response (defined as organ improvement of at least 1 stage without worsening in any other organ) OR a mixed response (defined as improvement in at least 1 evaluable organ with worsening in another); AND
    • Patient will require treatment with four additional (weekly) doses; OR
  • Patient is experiencing an aGVHD flare after achieving a complete response [CR]); AND
    • Patient will require treatment with eight additional (twice weekly) doses

Note: Patients who experience a complete response (defined as resolution of aGVHD in all involved organs) OR no response, may not renew coverage and will be reviewed on a case-by-case basis.

5. Dosage/Administration ^{1,3,7,21-23,25}

6. Billing Code/Availability Information

HCPCS Code:

• J3590 — Unclassified biologics

NDC:

• Ryoncil target 25 x 10⁶ MSCs in 3.8 mL in a single-dose vial: 73648-0154-xx

7. References

1. Ryoncil [package insert]. New York, NY; Mesoblast, Inc. December 2025. Accessed December 2025.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) for remestemcel-L. National Comprehensive Cancer Network, 2025. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed January 2025.
3. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) for Hematopoietic Cell Transplantation (HCT) Version 1.2025. National Comprehensive Cancer Network, 2025. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed January 2025.
4. ClinicalTrials.gov. NCT02336230. A Single-arm, Prospective Study of Remestemcel-L, Ex-vivo Culture-Expanded Adult Human Mesenchymal Stromal Cells, for the Treatment of Pediatric Patients Who Have Failed to Respond to Steroid Treatment for Acute GVHD. | ClinicalTrials.gov.

5. ClinicalTrials.gov. NCT00366145. A Phase III, Randomized, Double Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Prochymal® (Ex-vivo Cultured Adult Human Mesenchymal Stem Cells) Infusion for the Treatment of Patients Who Have Failed to Respond to Steroid Treatment for Acute GVHD. | ClinicalTrials.gov.
6. Kurtzberg J, Abdel-Azim H, Carpenter P, et al; MSB-GVHD001/002 Study Group. A Phase 3, Single-Arm, Prospective Study of Remestemcel-L, Ex Vivo Culture-Expanded Adult Human Mesenchymal Stromal Cells for the Treatment of Pediatric Patients Who Failed to Respond to Steroid Treatment for Acute Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2020 May;26(5):845-854. doi: 10.1016/j.bbmt.2020.01.018. Epub 2020 Feb 1
7. Kebriaei P, Hayes J, Daly A, et al. A Phase 3 Randomized Study of Remestemcel-L versus Placebo Added to Second-Line Therapy in Patients with Steroid-Refractory Acute Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2020 May;26(5):835-844. doi: 10.1016/j.bbmt.2019.08.029. Epub 2019 Sep 7. PMID: 31505228; PMCID: PMC7060124..

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

The preceding information is intended for non-Medicare coverage determinations. Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA): N/A