CurrentCentenePolicy CP.PHAR.301

Erwinia Asparaginase (Rylaze) Coverage

Defines medical necessity criteria, dosing limits, approvals, and continuation rules for coverage of Rylaze (Erwinia asparaginase) for Centene lines of business (Commercial, HIM, Medicaid). Applies to prescribers requesting authorization for the drug.

Policy Summary

PayerCentene

PolicyErwinia Asparaginase (Rylaze) Coverage

Policy CodePolicy CP.PHAR.301

Change TypeNo material changes

Effective DateFeb 1, 2017

Next Review Date

Key ActionSubmit documentation (office chart notes, lab results, or other clinical information) demonstrating the member meets all approval criteria for prior authorization.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

3Distinct covered indications specified

25 mg/m2Typical dose unit

50 mg/m2Max per-dose limit

12m / 6mApproval durations

J9021, J9019HCPCS codes referenced

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Initial Therapy - ALL

Covered when ALL of the following are met

ALL initial approval criteria: 1. Diagnosis of acute lymphoblastic leukemia (ALL); 2. Prescribed by or in consultation with an oncologist or hematologist; 3. Age >= 1 month; 4. Prescribed as a component of a multi-agent chemotherapeutic regimen; 5. Member has developed hypersensitivity to an E. coli–derived asparaginase product (e.g., Elspar, pegaspargase/Oncaspar, or calaspargase pegol/Asparlas); 6. Request meets one of the following dosing options: a) Dose does not exceed 25 mg/m2 every 48 hours; b) Dose does not exceed 25 mg/m2 on Monday and Wednesday and 50 mg/m2 on Friday; or c) Dose is supported by practice guidelines or peer‑reviewed literature for the requested use (prescriber must submit supporting evidence). Prescribed regimen must be FDA‑approved or recommended by NCCN.

Approval duration: Medicaid/HIM - 12 months; Commercial - 6 months or duration of request, whichever is less

Initial Therapy - LBL

Covered when ALL of the following are met

LBL initial approval criteria: 1. Diagnosis of lymphoblastic lymphoma (LBL); 2. Prescribed by or in consultation with an oncologist or hematologist; 3. Age >= 1 month; 4. Prescribed as a component of a multi-agent chemotherapeutic regimen; 5. Member has developed hypersensitivity to an E. coli–derived asparaginase product (e.g., Elspar or pegaspargase/Oncaspar); 6. Request meets one of the following dosing options: a) Dose does not exceed 25 mg/m2 every 48 hours; b) Dose does not exceed 25 mg/m2 on Monday and Wednesday and 50 mg/m2 on Friday; or c) Dose is supported by practice guidelines or peer‑reviewed literature for the requested use (prescriber must submit supporting evidence). Prescribed regimen must be FDA‑approved or recommended by NCCN.

Approval duration: Medicaid/HIM - 12 months; Commercial - 6 months or duration of request, whichever is less

Initial Therapy - Extranodal NK/T-cell lymphoma (off-label)

Covered when ALL of the following are met (off-label)

Extranodal NK/T-cell lymphoma criteria: 1. Diagnosis of extranodal NK/T‑cell lymphoma; 2. Prescribed by or in consultation with an oncologist or hematologist; 3. Age >= 18 years; 4. Member has developed hypersensitivity to an E. coli–derived asparaginase product (e.g., Elspar or pegaspargase/Oncaspar); 5. Dose is within the FDA maximum limit for any FDA‑approved indication or is supported by practice guidelines or peer‑reviewed literature for the requested off‑label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA‑approved or recommended by NCCN.

Approval duration: Medicaid/HIM - 12 months; Commercial - 6 months or duration of request, whichever is less

Continued Therapy

Continued therapy covered when ALL of the following are met

Continued therapy criteria: 1. Currently receiving medication via Centene benefit, or documentation supports the member is currently receiving Rylaze for a covered indication and has received at least 30 days of therapy; 2. Member is responding positively to therapy; 3. If the request is for a dose increase, the new dose meets one of the following: a) Dose does not exceed 25 mg/m2 every 48 hours; b) Dose does not exceed 25 mg/m2 on Monday and Wednesday and 50 mg/m2 on Friday; or c) New dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA‑approved or recommended by NCCN.

Approval duration: Medicaid/HIM - 12 months; Commercial - 6 months or duration of request, whichever is less

Non‑FDA approved indications that are not specifically addressed in this policy are not authorized unless the provider submits sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policy (see CP.CPA.09 for Commercial, HIM.PA.154 for Health Insurance Marketplace, or CP.PMN.53 for Medicaid). If the requested use is not listed in the Diagnoses/Indications section and does not meet other policy criteria, the request will be evaluated under the relevant off‑label policy requirements.

The discontinued Erwinaze product has been removed from the policy as a legacy product; administrative updates are recorded in the policy history. Per the prescribing information and the 1Q2025 review, severe hepatic impairment was added to the contraindications section and the change is reflected in the policy documentation and references.

Use of Rylaze (or Erwinia asparaginase) for non‑FDA approved indications that are not supported by sufficient clinical evidence is considered not authorized. Requests for off‑label use must include documentation demonstrating efficacy and safety consistent with the off‑label use policy for the member's line of business; absent such evidence, coverage will be denied.

Initial Therapy Criteria

Initial therapy

Initial therapy nodes: Initial coverage requires diagnosis appropriate to the indication, prescribing or consult by an oncologist/hematologist, applicable age criteria, use as part of a multi‑agent chemotherapy regimen (where specified), documentation of hypersensitivity to an E. coli‑derived asparaginase product, and dosing within specified limits or supported by practice guidelines/peer‑reviewed literature. Prescribed regimen must be FDA‑approved or recommended by NCCN.

Initial therapy notes

Policy history notes product preferences per NCCN

Product preference during induction (historical): In 1Q2022 the policy specified only Erwinaze recommended for ALL induction therapy per NCCN (historical note).

Continuation Therapy Criteria

Continuation therapy

Continuation nodes: See Continued Therapy criteria: member must be receiving medication for >= 30 days with a positive clinical response; any requested dose increases must meet dosing limits or be supported by practice guidelines/peer‑reviewed literature (prescriber must submit evidence).

Approval duration (Medicaid/HIM)

Policy administrative updates

Approval duration change for Medicaid/HIM: For Medicaid/HIM lines of business, initial and continued therapy approval durations were extended from 6 to 12 months for this maintenance medication.

Recorded in 1Q2026 annual review

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Providers must obtain prior authorization and submit clinical documentation demonstrating the member meets all applicable approval criteria (diagnosis, specialist involvement, age, hypersensitivity to E. coli–derived asparaginase products or listed alternatives, dosing limits or guideline-supported off‑label dosing, and that the prescribed regimen is FDA‑approved or NCCN‑recommended where required). Failure to provide sufficient documentation supporting the approval criteria or use for non‑FDA indications without adequate off‑label evidence may result in denial.

Prior authorization required per this clinical policy.
Requests must document diagnosis, treating specialist (oncologist/hematologist) involvement, age criteria, hypersensitivity history, regimen context (multi‑agent chemotherapy), and dosing justification or supporting literature for off‑label dosing.

Billing Rule

Claims Coding and HCPCS Guidance

Submit claims using the appropriate HCPCS code that corresponds to the product administered. Inclusion or exclusion of codes in this policy does not guarantee coverage; providers should verify current professional coding guidance prior to claim submission. The HCPCS code list in this policy is informational and has been updated over time (see policy history).

Use HCPCS J9021 for Rylaze (asparaginase, recombinant), 0.1 mg — bill units per product-specific strength.
Use HCPCS J9019 for Erwinaze (asparaginase), 1,000 IU — bill units per product-specific strength.
Policy HCPCS lists have been revised in reviews; J9020 was removed in 1Q2026 — verify current code set before billing.

Documentation Required

Required Documentation; Insufficiency Risk

Providers must supply supporting documentation with prior authorization requests. Acceptable documentation includes office chart notes, laboratory results, pathology reports, hospital discharge summaries, and other clinical information that supports the member has met all approval criteria. If documentation is incomplete or does not substantiate the requested indication, dose, or prior hypersensitivity to E. coli–derived products (or adequate off‑label evidence), the request may be denied.

Attach office/clinic notes describing diagnosis and treatment plan.
Include lab results, allergy/hypersensitivity documentation, and relevant prior therapy records (e.g., prior E. coli–derived asparaginase exposure and hypersensitivity event).
For off‑label uses, include peer‑reviewed literature or guideline references that support the requested regimen.

Step Therapy

Step Therapy / Therapy Sequencing Note

Step therapy: there is no specified medication trial sequence requiring trial of alternative agents prior to approval. Instead, coverage for Rylaze/Erwinaze requires documented hypersensitivity to E. coli–derived asparaginase products (or other specified criteria per indication) rather than a mandated step‑through of specific products. Provider should document the hypersensitivity event and rationale for product selection.

No explicit step‑therapy sequence; approval hinges on documented hypersensitivity to E. coli–derived asparaginase (Elspar, Oncaspar, Asparlas as listed) or meeting other stated criteria.
Historical product-specific recommendations (e.g., Erwinaze for certain induction settings) are in the policy history and may affect clinical expectations — consult current policy language and NCCN guidance.

Coding

HCPCS Codes referencedHCPCS

J9019	Injection, asparaginase, (Erwinaze), 1,000 IU
J9021	Injection, asparaginase, recombinant, (Rylaze), 0.1 mg

Step Therapy / Prior Therapy Requirements

Step	Requirement
1	Coverage contingent on development of hypersensitivity to an E. coli–derived asparaginase product (e.g., Elspar, pegaspargase/Oncaspar, calaspargase pegol/Asparlas for ALL); prior hypersensitivity must be documented — policy does not require a sequence of prior therapy failures.

Step	Policy note / history
1	Policy history records product-specific sequencing recommendations and updates (example: 1Q2022 specified Erwinaze for ALL induction per NCCN; 1Q2024 added Asparlas to the list of E. coli-derived asparaginase alternatives for hypersensitivity cases and removed a discontinued Erwinaze product).

Quantity Limits

Rylaze — Maximum 50 mg/m2 per dose

DrugRylaze (asparaginase recombinant, Erwinia)

Maximum per‑dose limit50 mg/m2 per dose

Typical replacement IM regimen25 mg/m2 IM every 48 hours OR 25 mg/m2 IM Monday and Wednesday and 50 mg/m2 IM on Friday

Rylaze — Maximum 50 mg/m2 per dose

Quantity limitMaximum 50 mg/m2 per dose

ContextApplies to ALL and LBL dosing regimens when replacing a long‑acting asparaginase product

Dose regimens referenced25 mg/m2 IM every 48 hours; or 25 mg/m2 IM Mon & Wed and 50 mg/m2 IM Fri

Definitions

ALL — acute lymphoblastic leukemia

AbbreviationALL = acute lymphoblastic leukemia

Coverage age minimum≥ 1 month for initial approval (per policy criteria)

Typical useComponent of multi‑agent chemotherapy for patients with hypersensitivity to E. coli‑derived asparaginase

LBL — lymphoblastic lymphoma

AbbreviationLBL = lymphoblastic lymphoma

Coverage age minimum≥ 1 month for initial approval (per policy criteria)

Typical useComponent of multi‑agent chemotherapy for patients with hypersensitivity to E. coli‑derived asparaginase

Rylaze replacement dosing (ALL, LBL)

Replacement regimen option 125 mg/m2 IM every 48 hours

Replacement regimen option 225 mg/m2 IM Monday and Wednesday, and 50 mg/m2 IM Friday

Maximum per dose50 mg/m2 per dose

Site of Care

Note

No explicit site‑of‑care restriction stated

No site‑of‑care restriction is specified in the site‑of‑care section of this policy.

The policy does not impose an infusion center or other site restriction for administration.

Background

Rylaze (asparaginase Erwinia chrysanthemi recombinant‑rywn) is an asparagine‑specific enzyme indicated for use as part of multi‑agent chemotherapy in patients who have developed hypersensitivity to E. coli‑derived asparaginase products. The policy covers Rylaze for acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in patients aged ≥ 1 month who meet the listed criteria, and includes an off‑label coverage pathway for extranodal NK/T‑cell lymphoma in adults ≥ 18 years with documented hypersensitivity and supporting dosing evidence. Prior authorization requires clinical documentation that the member meets diagnosis, specialist involvement, age, hypersensitivity to an E. coli‑derived asparaginase, and dosing limits or supportive literature; administrative updates to coding and contraindications are noted in the policy history.

Policy Summary

PayerCentene

PolicyErwinia Asparaginase (Rylaze) Coverage

Policy CodePolicy CP.PHAR.301

Change TypeNo material changes

Effective DateFeb 1, 2017

Next Review Date

Key ActionSubmit documentation (office chart notes, lab results, or other clinical information) demonstrating the member meets all approval criteria for prior authorization.

SourceLink

On This Page

OpenPayer

Erwinia Asparaginase (Rylaze) Coverage

Coverage Criteria

Initial Therapy Criteria

Continuation Therapy Criteria

Provider Actions and Requirements

Coding

Step Therapy / Prior Therapy Requirements

Quantity Limits

Definitions

Site of Care

Background