ModifiedBlue Cross Blue Shield - MassachusettsPolicy 028

Adjunct Medications to Support Hematopoietic Stem Cell Transplantation and its Complications

Clinical coverage criteria, prior authorization and coding guidance for Omidubicel (Omisirge) and Ryoncil for Blue Cross Blue Shield of Massachusetts members; applies to commercial and Medicare product lines described. Affects providers requesting authorization for these cellular therapies.

Policy Summary

PayerBlue Cross Blue Shield - Massachusetts

PolicyAdjunct Medications to Support Hematopoietic Stem Cell Transplantation and its Complications

Policy CodePolicy 028

Change TypeUpdated to include Ryoncilprior authorization requirements added

Effective Date

Next Review Date

Key ActionObtain prior authorization using Authorization Manager and submit required clinical documentation (enter facility and servicing provider NPIs).

SourceLink

POLICY UPDATE CHANGES

Updated policy, including Description and References sections, to include Ryoncil from July 2025 P&T and adjusted policy name to 'Adjunct Medications to Support Hematopoietic Stem Cell Transplantation and its Complications'.

Policy revised to include medically necessary and investigational indications; prior authorization is required effective 4/1/2024.

New medical policy added in 1/2024 describing investigational indications; Omidubicel considered investigational for certain indications.

Clarified coding information.

onetreatment course limit per lifetime for Omidubicel

12 vs 22 daysmedian time to neutrophil engraftment Omidubicel vs standard UCBT

39 vs 52

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 and Indications

Omidubicel (Omisirge) Initial Therapy

Omidubicel (Omisirge) is considered medically necessary when ALL of the following are met:

Omidubicel initial approval criteria: Individual is 12 years of age or older AND has a diagnosis of hematologic malignancy and is planned for umbilical cord blood transplantation following myeloablative conditioning to reduce time to neutrophil recovery and incidence of infection AND is a candidate for myeloablative allogeneic hematopoietic stem cell transplantation (HSCT)

One treatment course per lifetime (single one-time infusion)

Exclusion conditions for Omidubicel: Individual does not have any of the following: availability of an HLA-identical, HLA-matched, or HLA-haploidentical donor; history of prior allogeneic hematopoietic stem cell transplant; other malignancy or significant immunodeficiency disorder; active, uncontrolled HCV or HBV infection

If any exclusion is present, Omidubicel is investigational for that indication

Prescriber requirement: Medication is being prescribed by or in consultation with a hematologist/oncologist

Ryoncil Initial Therapy

Ryoncil (remestemcel-L-rknd) is considered medically necessary when ALL of the following are met:

Ryoncil initial approval criteria: Diagnosis of steroid-refractory acute graft-versus-host disease (SR-aGvHD) AND age ≥ 2 months AND aGvHD progressed within 3 days or did not improve within 7 consecutive days of treatment with methylprednisolone 2 mg/kg/day or other corticosteroid equivalent

Dosage and administration per Ryoncil prescribing information; continuation guided by Day 28 response rules (no further treatment for complete response; additional weekly infusions for partial/mixed response; alternate treatments for no response)

Coverage notes and high‑level stances

Policy-level statements and high‑level stances related to these therapies (prior authorization, inclusion of Ryoncil, investigational notes):

Prior authorization requirement: Prior authorization is required for coverage decisions for the therapies and indications addressed in this policy

Precertification/preauthorization is required for inpatient services; outpatient prior authorization is required as indicated

Inclusion of Ryoncil: Ryoncil (remestemcel-L) was added to the policy following July 2025 Pharmacy & Therapeutics and is included for treatment of pediatric steroid-refractory aGvHD with trial evidence showing 70% ORR at day 28

Refer to prescribing information and trial MSB-GVHD-001 for dosing and response rules

Omidubicel investigative stance: Omidubicel is identified in the policy history as investigational for individuals with hematologic malignancies planning myeloablative allogeneic umbilical cord transplantation if they do not meet the specific policy criteria

Continuation of Omidubicel therapy is not covered; approval limited to one treatment course per lifetime

Omidubicel (Omisirge®) is considered investigational when the patient does not meet the specific policy criteria for initial approval or when used for any indication not explicitly covered by this policy. The policy text specifies that Omidubicel is investigational for individuals who do not meet the listed criteria and for all other indications outside the approved coverage conditions.

Continuation dosing for Ryoncil (remestemcel‑L‑rknd) should follow the prescribing information: no further treatment is recommended for Complete Response at Day 28; for Partial or Mixed Response repeat administration once weekly for up to an additional 4 weeks (total 4 infusions); for No Response consider alternative treatments; and for Recurrence after complete response repeat administration twice weekly for an additional 4 consecutive weeks (up to 8 infusions total).

The policy identifies Omidubicel as investigational for use in individuals with hematologic malignancies who are planning myeloablative allogeneic umbilical cord blood transplantation, per the policy history and the investigational/coverage statements.

Approval for Omidubicel is limited to a single treatment course per lifetime. The policy explicitly states continuation of therapy is not a covered service and that quantity limits restrict use to one treatment course per lifetime.

This policy includes investigational indications and explicitly lists specific interventions identified as investigational. Notably, Omidubicel is called out as investigational for certain transplant indications, and the policy history documents the addition and clarification of investigational and coverage stances over time.

Covered Regimens and Dosing

Regimen	Coverage stance	Key details / Rationale
Omidubicel‑modified umbilical cord blood transplant (single one‑time infusion; one treatment course per lifetime)
Omidubicel is intended to accelerate neutrophil recovery and reduce early transplant‑related infections compared with standard UCB transplantation; pivotal phase 3 randomized trial (N=125; Omidubicel N=62 vs standard UCBT N=63) demonstrated median time to neutrophil engraftment 12 days vs 22 days, higher neutrophil engraftment (96% vs 89%), fewer grade 2–3 bacterial or invasive fungal infections, and shorter hospital stay (39 days vs 52 days)
Use limited to a single treatment course per lifetime; intended for patients undergoing myeloablative conditioning and UCB transplantation

Regimen	Coverage stance	Key details / Continuation rules
Ryoncil (remestemcel‑L‑rknd) per prescribing information
Indicated for steroid‑refractory acute graft‑versus‑host disease (SR‑aGvHD); initial approval criteria include diagnosis of SR‑aGvHD and age ≥ 2 months; refer to Ryoncil prescribing information for dosing and administration
Continuation: additional doses may be considered per prescribing label based on Day 28 response — no further treatment for complete response; repeat once weekly for 4 weeks for partial/mixed response; consider alternatives for no response; repeat twice weekly x4 weeks for recurrence after complete response

Regimen	Coverage stance	Dose / Schedule and additional infusions
Remestemcel‑L (Ryoncil) — pediatric dosing regimen
Dose: 2 x 10^6 MSCs/kg per infusion; schedule: twice weekly for 4 weeks (2 infusions/week for 4 weeks = 8 infusions)
Patients with partial or mixed response at Day 28: additional infusions once weekly for 4 weeks; patients with recurrence after complete response: additional infusions twice weekly for 4 weeks

Agent	Coverage stance	Notes
Ruxolitinib
FDA‑approved, Category 1 agent listed in policy
Included as an FDA Approved, Category 1 agent for management of relevant transplant‑related complications

Agent / Therapy	Coverage stance	Notes
Alemtuzumab
Alpha‑1 antitrypsin
ATG (anti‑thymocyte globulin)
Basiliximab
Calcineurin inhibitors (e.g., tacrolimus, cyclosporine)
Etanercept
Extracorporeal photopheresis (ECP)
Infliximab
mTOR inhibitors (e.g., sirolimus)
Mycophenolate mofetil
Pentostatin
Tocilizumab
Urinary‑derived hCG/EGF
Vedolizumab

Billing and Coding

HCPCS CodesHCPCSCovered

J3402	Injection, remestemcel-l-rknd, per therapeutic dose.
J3590	Unclassified biologics.
C9399	Unclassified drugs or biologicals

CPT/HCPCS/ICD codesmixed

No codes listed

inv-11: Age threshold for Omidubicel

Age threshold>= 12 years

Applies toOmidubicel (Omisirge) initial approval criteria for one-time infusion

ContextPatients planned for umbilical cord blood transplantation following myeloablative conditioning

inv-12: Age threshold for Ryoncil

Age threshold>= 2 months

Applies toRyoncil (remestemcel-L-rknd) initial approval criteria

Provider Actions, Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior Authorization Required. Preauthorization is required for inpatient services described in this policy and for outpatient administration across commercial and Medicare product lines. Failure to obtain prior authorization may result in denial of payment.

Inpatient services: precertification/preauthorization IS REQUIRED for all products when performed inpatient.
Outpatient services: prior authorization is required for Commercial Managed Care (HMO and POS), Commercial PPO and Indemnity, Medicare HMO Blue SM, and Medicare PPO Blue SM.

Documentation Required

How to Request Prior Authorization

Providers must submit authorization requests using Authorization Manager. Enter the facility's NPI or provider ID where services will be performed and enter the servicing provider's NPI (the surgeon or treating provider), not the billing group. For out-of-network providers, fax requests to 888-973-0726.

Line of Therapy Designations

not_specified

Use context: Omidubicel is intended for patients undergoing myeloablative conditioning and umbilical cord blood (UCB) transplantation who lack a matched sibling or unrelated donor

Designed to accelerate neutrophil recovery and reduce infection risk

salvage

Ryoncil use (salvage): Treatment is intended as salvage therapy for steroid-refractory acute graft-versus-host disease (SR-aGvHD); clinical trial dosing and Day 28 response rules apply

Line of therapy: salvage for SR-aGvHD; pediatric trial MSB-GVHD-001 showed 2 x 10^6 MSCs/kg twice weekly x4 weeks with additional infusions per response

Definitions and Key Terms

inv-24: Omidubicel (Omisirge) definition and product description

Product name (trade)Omisirge (omidubicel)

DefinitionA nicotinamide-modified allogeneic hematopoietic progenitor cell therapy derived from cord blood using proprietary nicotinamide enrichment/expansion technology

Indication contextIntended to accelerate neutrophil recovery and reduce incidence of infection in patients with hematologic malignancies undergoing myeloablative conditioning and umbilical cord blood transplant

Treatment course limitOne treatment course per lifetime (one-time infusion for initial approval)

inv-25: Ryoncil (remestemcel-L-rknd) definition and product description

Product name (trade)

Background and Clinical Context

Hematologic malignancies are a heterogeneous group of diseases for which hematopoietic cell transplantation (autologous or allogeneic) may be required. When matched donors are unavailable, umbilical cord blood (UCB) can serve as an alternative graft source, but UCB transplants have limitations such as lower cell dose for larger recipients and delayed neutrophil engraftment. Omidubicel is a nicotinamide‑modified, expanded UCB‑derived allogeneic hematopoietic progenitor cell therapy developed to enhance engraftment and accelerate neutrophil recovery compared with standard UCB transplantation.