CurrentBlue Cross Blue Shield - North CarolinaPolicy N/A

Remestemcel-L-rknd (Ryoncil) IV infusion for pediatric steroid-refractory acute GVHD

Defines medical necessity, approval criteria, dosing limits, and authorization requirements for remestemcel-L-rknd (Ryoncil) intravenous infusion in pediatric patients with steroid-refractory acute graft-versus-host disease; applies to Blue Cross NC coverage decisions and providers seeking authorization.

Policy Summary

PayerBlue Cross Blue Shield - North Carolina

PolicyRemestemcel-L-rknd (Ryoncil) IV infusion for pediatric steroid-refractory acute GVHD

Policy CodePolicy N/A

Change TypeCoding and administrative updates (HCPCS J3402 addedrevenue codes and distribution language added)

Effective DateApr 1, 2026

Next Review DateApr 1, 2026

Key ActionObtain prior authorization using HCPCS J3402 with initial approval for 30 days and document steroid-refractory status, IBMTR grading, organ involvement, prior steroid therapy, and prescriber specialty.

SourceLink

POLICY UPDATE CHANGES

Added applicable revenue codes 0891 and 0892 associated with policy HCPCS code(s).

Added Gene/Cellular Therapy distribution channel management language according to benefit booklet.

Added HCPCS J3402 as the specific code for remestemcel-L-rknd (1 unit per therapeutic dose) and removed miscellaneous J-codes.

Removed Site of Care medical necessity criteria.

2 months to <18 yrsAge range eligible for coverage

8Initial treatment limit

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage criteria for remestemcel-L-rknd (Ryoncil)

inv-01: Initial Therapy

Covered when ALL of the following are met:

Initial Approval: 1) The patient is 2 months to less than 18 years of age; AND 2) Diagnosis of steroid-refractory acute graft-versus-host disease (SR-aGVHD) with medical record documentation; AND 2a) IBMTR severity grade B, C, or D per IBMTR Severity Index Criteria (documentation required); AND 2b) Symptoms involving skin, liver, and/or gastrointestinal tract (documentation required); AND 2c) The patient does NOT have grade B aGVHD with skin-only involvement (documentation required); AND 3) Failed first-line systemic steroid treatment, defined as disease progression within 3 days or no improvement within 7 days of consecutive treatment with methylprednisolone 2 mg/kg/day or equivalent (documentation required); AND 4) Post-allogeneic hematopoietic stem cell transplantation (HSCT) (documentation required); AND 5) For patients 12 to less than 18 years, ONE of: (a) Trial and inadequate response to ruxolitinib, OR (b) Intolerance, FDA-labeled contraindication, or hypersensitivity to ruxolitinib (documentation required); AND 6) No evidence of encephalopathy, diffuse alveolar hemorrhage, or other active pulmonary disease (documentation required); AND 7) No known hypersensitivity to dimethyl sulfoxide (DMSO) or murine, porcine, or bovine proteins (documentation required); AND 8) Prescriber is a specialist in the area of the patient's diagnosis (e.g., oncologist, hematologist, transplant specialist) or has consulted with such a specialist (documentation required); AND 9) Requested dose is within FDA-labeled dosing for the indication and requested quantity does not exceed maximum units allowed for the duration of approval (documentation required); AND 10) The patient will not receive more than 8 infusions total for initial treatment (documentation required).Age and prior treatment requirements

Medical record documentation required for each element.

inv-02: Continuation Therapy

Covered when ALL of the following are met after initial approval:

Continuation Approval: 1) Patient was approved through Blue Cross NC initial criteria for approval OR would have met initial criteria at therapy start; AND 2) Patient is less than 18 years of age; AND 3) Patient does NOT have unacceptable toxicity from the requested agent (e.g., severe infusion-related or hypersensitivity reactions) (documentation required); AND 4) Patient has ONE of the following responses following the initial 8 infusions (documentation required): (a) Partial response (PR): organ improvement of ≥1 stage without worsening in any other organ per IBMTR — then patient will require 4 additional weekly infusions over four consecutive weeks AND must start the 9th infusion within 7 days of completing the 8th; OR (b) Mixed response (MR): improvement in ≥1 organ stage with worsening in another per IBMTR — then patient will require 4 additional weekly infusions over four consecutive weeks AND must start the 9th infusion within 7 days of completing the 8th; OR (c) Recurrence of grade B, C, or D aGVHD after prior complete resolution — then patient will require 8 additional twice-weekly infusions over four consecutive weeks; AND 5) No evidence of encephalopathy, diffuse alveolar hemorrhage, or other active pulmonary disease (documentation required); AND 6) Prescriber is a specialist in the area of the patient's diagnosis or has consulted with a specialist (documentation required); AND 7) Requested dose is within FDA-labeled dosing for the indication and requested quantity does not exceed maximum units allowed for the duration of approval; AND 8) Patient has NOT received more than 16 infusions total (documentation required).Response-based continuation and timing

Medical record documentation required for response and timing.

The therapy is not indicated for patients with grade B aGVHD with skin-only involvement. Requests should also be declined when the patient has encephalopathy, diffuse alveolar hemorrhage or other active pulmonary disease, or a known hypersensitivity to dimethyl sulfoxide (DMSO) or to murine, porcine, or bovine proteins. Medical record documentation is required for these findings and is necessary to support a denial when present.

Assess response at approximately day 28 ± 2 days after initiating therapy. A documented complete response at day 28 requires no further Ryoncil treatment. For documented partial (PR) or mixed responses (MR), continue therapy with 4 additional weekly infusions (beginning such that the 9th infusion starts within 7 days of completing the 8th initial infusion). If there is no response after the initial treatment course, consider alternative therapies rather than continuing Ryoncil. For recurrence of grade B–D aGVHD after prior complete resolution, retreatment consists of 8 additional twice-weekly infusions over 4 weeks.

Dosing and administration

Dose	Initial schedule	Assessment timing	Actions based on day 28 response	Continuation / Recurrence dosing	Maximum infusions (initial / lifetime)
2 x 10^6 mesenchymal stromal cells (MSC)/kg per infusion
Twice weekly (at least 3 days apart) for 4 consecutive weeks (8 infusions total)
Assess response 28 ± 2 days after first dose
Complete response: no further Ryoncil treatment; Partial or mixed response: repeat treatment once weekly for an additional 4 consecutive weeks (4 infusions total); No response: consider alternative treatments
Recurrence following complete response: 8 additional twice-weekly infusions over 4 weeks
Initial: 8 infusions; Lifetime maximum: up to 16 infusions

Billing and coding

Applicable HCPCS CodesHCPCSCovered

J3402

remestemcel-L-rknd, 1 unit per therapeutic dose

Applicable Revenue CodesRevenue

0891	Special Processed Drugs - FDA Approved Cell Therapy (revenue)
0892	Special Processed Drugs - FDA Approved Gene Therapy (revenue)

Previously Used Miscellaneous Codes (termed)HCPCSNot Covered

C9399	Other drugs or biologics (deleted 9/30/2025)
J3490	Unclassified drugs (deleted 9/30/2025)
J3590	Unclassified biologics (deleted 9/30/2025)
J9999	Not Otherwise Classified (deleted 9/30/2025)

Maximum infusions — inv-08: Ryoncil (remestemcel-L-rknd) infusion limits

Initial treatment limit8 infusions total per initial authorization

Continuation (partial/mixed response)Up to 4 additional weekly infusions (start 9th infusion within 7 days of completing 8th)

Continuation (recurrence after CR)8 additional twice-weekly infusions over 4 weeks

Lifetime maximumMaximum of 16 infusions total per lifetime

What providers must do to obtain coverage

Prior Authorization

Prior Authorization Required

Prior authorization required. Initial approval duration is 30 days. Initial authorization allows up to 8 infusions; lifetime maximum is 16 infusions. Bill using HCPCS code J3402.

Initial approval: 30 days; up to 8 infusions
Lifetime maximum: 16 infusions
Billing code: HCPCS J3402

Step Therapy

Pediatric Step Requirement (12 to <18 years)

For patients aged 12 to less than 18 years, the prescriber must document that the patient has either: (a) tried ruxolitinib and had an inadequate response, or (b) is intolerant to, has an FDA‑labeled contraindication to, or has hypersensitivity to ruxolitinib. Medical record documentation is required.

Document trial and inadequate response to ruxolitinib OR intolerance/contraindication/hypersensitivity to ruxolitinib
Applicable only to patients 12 to <18 years

Role in therapy

inv-16: salvage

Post-HSCT setting: Use is indicated post-allogeneic HSCT for steroid-refractory acute GVHD in pediatric patients; considered after failure of first-line systemic steroids (salvage-line therapy).

Key definitions used in this policy

Steroid-refractory acute GVHD (SR-aGVHD) — inv-14

DefinitionFailure to respond to first-line systemic steroid treatment defined as disease progression within 3 days or no improvement within 7 days of consecutive treatment with methylprednisolone 2 mg/kg/day or equivalent.

ContextApplies to diagnosis of steroid-refractory acute graft-versus-host disease (SR-aGVHD) following allogeneic HSCT.

DocumentationMedical record documentation of steroid treatment and response timing is required for prior authorization.

IBMTR Severity Index Criteria — inv-15

IBMTR grading systemInternational Blood and Marrow Transplantation Registry (IBMTR) Severity Index Criteria used to classify aGVHD severity into grades B, C, or D.

Eligibility use

Background

Remestemcel-L-rknd (Ryoncil) is an FDA‑labeled intravenous mesenchymal stromal cell product indicated for the treatment of steroid‑refractory acute graft‑versus‑host disease (SR‑aGVHD) in pediatric patients aged ≥ 2 months to less than 18 years. The FDA dosing reference specifies 2 × 10^6 MSC/kg per infusion with an initial regimen of twice‑weekly infusions (at least 3 days apart) for 4 consecutive weeks (8 infusions total), and response assessment at day 28 ± 2 days to guide further treatment.