Medical Drug Criteria (MDC)

Policy Num:      P1.002.023
Policy Name:    Ryoncil (Remestemcel-L-rknd)
Policy ID:          [P1.002.023] [Ac L M+ P+ ]

Last Review:   September 22, 2025
Next Review:   September 20, 2026
 

Remestemcel-l-rknd (Ryoncil)

Summary

Remestemcel-L-rknd (Ryoncil) is FDA-approved for the treatment of steroid-refractory acute graftversus-host disease (SR-aGvHD) in pediatric patients greater than or equal to 2 months of age.  It contains  mesenchymal stromal cells (MSC) from the bone marrow of healthy human adult donors.  MSCs inhibit T-cell activation which have a role in the inflammatory response and organ damage associated with acute graft-versus-host disease (aGvHD).   

Policy Statements

Remestemcel-l-rknd (Ryoncil) is considered medically necessary for the treatment of steroid-refractory acute graft versus host disease (SR-aGvHD) in pediatric patients 2 months of age and older.  

Policy Guidelines

I. Initiation of remestemcel-l-rknd (Ryoncil) meets the definition of medical necessity for the following indications when ALL of the associated criteria are met:

1. Steroid refractory acute graft-versus-host disease (SRaGVHD) and ALL of the following– documentation must be submitted:

a. The individual is diagnosed with aGVHD following an allogeneic hematopoietic stem cell transplant.

b. The indicidual’s disease severity is classified as Grade B, C, or D according to the International Blood and Marrow Transplantation Registry (IBMTR) Severity Index Criteria.

c. The individual 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.

d. Individual 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

II. Continuation of remestemcel-l-rknd (Ryoncil) meets the definition of medical necessity when ALL of the following criteria are met:

1. An authorization or reauthorization for remestemcel-l-rknd has been previously approved by Triple S or another health plan in the past 2 years for the treatment of aGVHD, OR the individual has previously met ALL indication-specific criteria.

2. The indicidual has ONE of the following responses following the initial 8 doses of remestemcel-l-rknd– documentation must be submitted:

a. 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)

b. Mixed response (i.e., improvement of at least one organ with worsening in another organ per the IBMTR Severity Index Criteria)

c. 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 individual has not received more than 16 infusions total:

a. Partial or mixed response: 2 x 106 MSC/kg once a week for four consecutive weeks (4 infusions total).

b. 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 

DOSAGE/ADMINISTRATION

For intravenous use only.

RYONCIL is available as a cell suspension for intravenous infusion in a target concentration of 6.68 X 106 MSCs per mL in 3.8 mL contained in a 6 mL cryovial.

Recommended Dosage

The recommended dosage of RYONCIL is 2 × 106 mesenchymal stromal cells (MSC)/kg body weight per intravenous infusion given twice a week for 4 consecutive weeks for a total of 8 infusions. Administer infusions at least 3 days apart.  

 Assess response 28 ± 2 days after the first dose and administer further treatment as appropriate as described in Table 1 based on Day 28 response:

Table 1: Recommended Treatment based on Day 28 Response 

*Partial response defined as organ improvement of at least one stage without worsening in any other organ, whereas mixed response was defined as improvement of at least one evaluable organ with worsening in another organ as per International Blood and Marrow Transplantation Registry Severity Index Criteria grading system. 

REQUIRED MEDICAL INFORMATION

Pretreatment

Premedicate patients with corticosteroids and antihistamines 30-60 minutes prior to administration of RYONCIL to reduce the potential for infusion reactions.

Infusion Rates

• For patients weighing 35 kg or more, infuse RYONCIL at a rate of no more than 6mL/ minute.

• For patients weighing less than 35 kg, infuse RYONCIL over the course of 60 minutes. 

EXCLUSION CRITERIA

Known hypersensitivity to dimethyl sulfoxide (DMSO) or Porcine and Bovine proteins.  

Precautions/Warnings

Hypersensitivity/Acute Infusion reactions: Monitor for hypersensitivity reactions during infusion and premedicate with corticosteroids and antihistamines.

Transmission of Infectious Agents:  RYONCIL may transmit infectious agents.

Ectopic Tissue Formation: Ectopic tissue formation may occur following treatment with RYONCIL. 

BENEFIT APPLICATION

State or federal mandates (eg, Federal Employee Program) may dictate that certain U.S. Food and Drug Administration-approved devices, drugs, or biologics may not be considered investigational, and thus these devices may be assessed only by their medical necessity. 

Based on benefits or contract language, Remestemcel-l-rknd (Ryoncil) Infusion may be considered either a pharmacy or a medical benefit. 

Benefits are determined by the group contract, member benefit booklet, and/or individual subscriber certificate in effect at the time services were rendered.  Benefit products or negotiated coverages may have all or some of the services discussed in this medical policy excluded from their coverage.

OTHER CRITERIA

None available. 

Practice Guidelines and Position Statements

No Interqual Criteria Applicable.

Medicare National Coverage

There is no national coverage determination. In the absence of a national coverage determination, coverage decisions are left to the discretion of local Medicare carriers.

References

1. Remestemcel-l-rknd (Ryoncil) Infusion [package insert]. R-AGVHD Treatment | Pediatric Patients | Ryoncil.com. (2025). https://www.ryoncil.com/
2. Remestemcel-l-rknd (Ryoncil) Infusion. Florida Blue Coverage Guideline.  (2025). https://mcgs.bcbsfl.com/

Codes

Policy History