Background

Ryoncil, also known as remestemcel-L, is a mesenchymal stromal cell (MSC) therapy approved by the FDA for the treatment of steroid-refractory acute graft-versus-host disease (SR-aGvHD) in pediatric patients aged 2 months and older.

Policy (Criteria)

Ryoncil are considered MEDICALLY NECESSARY when ALL of the following criteria is met:

1. Steroid refractory acute graft-versus-host disease (SRaGVHD) and ALL of the following documentation must be submitted:
   1. The member is diagnosed with aGVHD following an allogeneic hematopoietic stem cell transplant
   2. Patient disease severity is classified as Grade B, C, or D according to the International Blood and Marrow Transplantation Registry (IBMTR) Severity Index Criteria
   3. Patient had an inadequate response to methylprednisolone 2 mg/kg/day or equivalent defined as disease progression within 3 days of treatment or no improvement within 7 consecutive days of treatment
   4. Patient is less than 18 years of age
2. Remestemcel-l-rknd is prescribed by or in consultation with an oncologist, hematologist, or transplant specialist
3. Dosage does not exceed 2 x 106 MSC/kg twice a week (at least 3 days apart) for four consecutive weeks (8 infusions total)

Approval duration: 1 month

Continuation of Ryoncil is considered MEDICALLY NECESSARY when the following criteria are met:

1. An authorization for remestemcel-l-rknd has been previously approved by health plan in the past 2 years for the treatment of aGVHD, OR the member has previously met ALL indication-specific criteria.
2. The member has ONE of the following responses following the initial 8 doses of remestemcel-l-rknd– documentation must be submitted:
   1. Partial response (i.e., organ improvement of at least one stage per the International  Blood and Marrow Transplantation Registry (IBMTR) Severity Index Criteria without worsening in any other organ)
   2. Mixed response (i.e., improvement of at least one organ with worsening in another organ per the IBMTR Severity Index Criteria)
   3. Recurrence of aGvHD following complete response (i.e., disease recurrence following a resolution of aGvHD in all involved organs)
3. Remestemcel-l-rknd is prescribed by or in consultation with an oncologist, hematologist, or transplant specialist
4. Dosage does not exceed ONE of the following and the member has not received more than 16 infusions total:
   1. Partial or mixed response: 2 x 106 MSC/kg once a week for four consecutive weeks (4 infusions total).
   2. Disease recurrence following complete response: 2 x 106 MSC/kg twice a week (at least 3 days apart) for four consecutive weeks (8 infusions total).

Approval duration: 1 month

References

1. Ryoncil (Remestemcel-L) [prescribing information]. New York, NY: Mesoblast, Inc; January 2025.
2. Ryoncil Billing and Coding Guide. New York, NY: Mesoblast, Inc; accessed 07/09/2025, Available at: Neryoncil-billing-coding-guide.pdf

Coding Section

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each Policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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