Last Review Date: 12/03/2024

Date of Origin: 08/03/2021

Dates Reviewed: 08/2021, 11/2021, 04/2022, 11/2022, 12/2022, 11/2023, 12/2024

1. Length of Authorization

Coverage will be provided for 6 months and may be renewed.

2. Dosing Limits

Max Units (per dose and over time) [HCPCS Unit]:

• 2,500 billable units (250 mg) per week

3. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

• Patient is at least 1 month of age; AND
• Patient must not have a history of serious pancreatitis, thrombosis, or hemorrhagic events with prior L-asparaginase therapy; AND

Universal Criteria ¹

• Patient must not have severe hepatic impairment; AND
• Used as a component of multi-agent chemotherapy regimen; AND
• Patient will receive premedication prior to administration of Rylaze to decrease the risk and severity of hypersensitivity reactions§ (e.g., acetaminophen, an H-1 receptor blocker [such as diphenhydramine], and an H-2 receptor blocker [such as famotidine]); AND

Acute Lymphoblastic Leukemia (ALL)/Lymphoblastic Lymphoma (LBL) † Ф ^1-3,5

• Used as a substitute for E. coli-derived asparaginase (e.g., pegaspargase, calaspargase) in cases of hypersensitivity (e.g., systemic allergic reactions or anaphylaxis) §

T-Cell Lymphomas ‡ ²

• Patient has Extranodal NK/T-Cell Lymphoma; AND
• Used as a substitute for pegaspargase in cases of systemic allergic reaction or anaphylaxis due to hypersensitivity to pegaspargase

† FDA Approved Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug

4. Renewal Criteria ¹

Coverage can be renewed based upon the following criteria:

• Patient continues to meet the universal and indication-specific criteria as identified in section III; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: severe hypersensitivity reactions including anaphylaxis, pancreatitis, thrombosis, hemorrhage, hepatotoxicity (including hepatic veno-occlusive disease), etc.; AND

Acute Lymphoblastic Leukemia (ALL)

• Disease stabilization or improvement as evidenced by a complete response [CR] (e.g., morphologic, cytogenetic or molecular complete response CR), complete hematologic response or a partial response by CBC, bone marrow cytogenic analysis, QPCR, or FISH

T-Cell Lymphoma

• Disease response with treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread

5. Dosage/Administration ¹

6. Billing Code/Availability Information

HCPCS Code:

• J9021 – Injection, asparaginase, recombinant, (rylaze), 0.1 mg; 1 billable unit = 0.1 mg

NDC(s):

• Rylaze 10 mg/0.5 mL solution in a single-dose vial: 68727-0900-xx

7. References

1. Rylaze [package insert]. Palo Alto, CA; Jazz Pharmaceuticals, Inc.; April 2024. Accessed November 2024.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) for Asparaginase Erwinia chrysanthemi (recombinant)-rywn. National Comprehensive Cancer Network, 2024. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed November 2024.
3. Pieters R, Hunger SP, Boos J, et al. L-asparaginase treatment in acute lymphoblastic leukemia: a focus on Erwinia asparaginase. Cancer. 2011 Jan 15; 117(2): 238–249.
4. Raetz EA, Salzer WL. Tolerability and Efficacy of L-Asparaginase Therapy in Pediatric Patients With Acute Lymphoblastic Leukemia, Journal of Pediatric Hematology/Oncology: October 2010 - Volume 32 - Issue 7 - p 554-563 doi: 10.1097/MPH.0b013e3181e6f003
5. Maese L, Rau RE, Raetz EA, et al. A phase II/III study of JZP-458 in patients with acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL) who are hypersensitive to E. coli-derived asparaginases. DOI: 10.1200/JCO.2020.38.15_suppl.TPS7568 Journal of Clinical Oncology 38, no. 15_suppl
6. Lin T, Hernandez-Illas M, Rey A, Jenkins J, et al. A Randomized Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Recombinant Erwinia Asparaginase (JZP-458) in Healthy Adult Volunteers. Clin Transl Sci. 2021 May;14(3):870-879. doi: 10.1111/cts.12947. Epub 2021 Mar 23.
7. Stock W, Douer D, DeAngelo DJ, et al. Prevention and management of asparaginase/pegasparaginase-associated toxicities in adults and older adolescents: recommendations of an expert panel. Leuk Lymphoma 2011:52;2237-2253.
8. Common Terminology Criteria for Adverse Events (CTCAE) v5.0. NIH National Cancer Institute: Division of Cancer Treatment & Diagnosis – Cancer Therapy Evaluation Program. Available at: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm#ctc_50.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

The preceding information is intended for non-Medicare coverage determinations. Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA): N/A