Medicare Advantage

Medical Policy

Notification

Asparaginase erwinia chrysanthemi (Erwinaze®), asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze®)

Notification Issue Date:

This version of the policy will become effective 12/16/2019.

The policy has been updated to communicate changes based on National Comprehensive Cancer Network (NCCN). Criteria have been revised to include use of Erwinase® as first-line therapy for adult individuals over 65 years of age and used in pediatric individuals with acute lymphoblastic leukemia.

Title:

Asparaginase erwinia chrysanthemi (Erwinaze®), asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze®)

Policy #:

MA08.085g

Policy

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member's medical needs and condition.

MEDICALLY NECESSARY

ASPARAGINASE ERWINIA CHRISANTHEMI (ERWINASE)

Acute Lymphoblastic Leukemia (ALL)

Asparaginase Erwinia chrysanthemi (Erwinaze) is considered medically necessary and, therefore, covered for the treatment of acute lymphoblastic leukemia (ALL) for the following indications:

As part of a multiagent chemotherapeutic regimen when all of the following criteria are met:

The individual is 1 year of age or older
Asparaginase Erwinia chrysanthemi (Erwinaze) is being used as a component of a multiagent chemotherapeutic regimen.
The individual has a history of documented hypersensitivity (i.e., systemic allergic reaction or anaphylaxis) to Escherichia coli–derived asparaginase (e.g., pegaspargase [Oncaspar], asparaginase [Elspar]).
The individual does not have any of the following contraindications:
- History of serious hypersensitivity reactions (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Grades 3 and 4) to asparaginase Erwinia chrysanthemi (Erwinaze), including anaphylaxis
- History of serious pancreatitis with prior L-asparaginase therapy manifested by abdominal pain for longer than 72 hours and amylase elevation greater than or equal to 2.0 times the upper limit of normal (ULN)
- History of serious thrombosis (e.g., sagittal sinus thrombosis or pulmonary embolism) with prior L-asparaginase therapy
- History of serious hemorrhagic events (NCI CTCAE Grade 4 with CNS involvement) with prior L-asparaginase therapy

As part of an induction therapy when all of the following criteria are met:

The individual is 65 years of age and older or individuals with substantial comorbidities
Asparaginase Erwinia chrysanthemi (Erwinaze) is being used as a component of one of the following:
- PETHEMA-based regimen such as ALLOLD07 (vincristine, dexamethasone, idarubicin, cyclophosphamide, cytarabine, methotrexate, and L-asparaginase) (moderate intensity) for Philadelphia chromosome–negative ALL
- Modified DFCI 91-01 protocol: dexamethasone, doxorubicin, vincristine, methotrexate, cytarabine, L-asparaginase, and IT chemotherapy) (moderate intensity) for Philadelphia chromosome–negative ALL
- EWALL: Tyrosine kinase inhibitor (TKI)* (e.g., bosutinib, dasatinib, imatinib, nilotinib, or ponatinib) with multiagent chemotherapy (vincristine, dexamethasone, methotrexate, cytarabine, asparaginase) (moderate intensity) for Philadelphia chromosome–positive ALL
The individual does not have any of the following contraindications:
- History of serious hypersensitivity reactions (NCI CTCAE Grades 3 and 4) to asparaginase Erwinia chrysanthemi (Erwinaze), including anaphylaxis
- History of serious pancreatitis with prior L-asparaginase therapy manifested by abdominal pain for longer than 72 hours and amylase elevation greater than or equal to 2.0 times the ULN
- History of serious thrombosis (e.g., sagittal sinus thrombosis or pulmonary embolism) with prior L-asparaginase therapy
- History of serious hemorrhagic events (NCI CTCAE Grade 4 with central nervous system [CNS] involvement) with prior L-asparaginase therapy

* TKI/mutation contraindications: Bosutinib - T315I, V299L, G250E, or F317L; Dasatinib - T315I/A, F317L/V/I/C or V299L; Imatinib too numerous to include; Nilotinib - T315I, Y253H, E255K/V, F359V/C/I or G250E. Ponatinib is a treatment option for individuals with a T315I mutation and/or for individuals for whom no other TKI is indicated.

ASPARAGINASE ERWINIA CHRISANTHEMI [RECOMBINANT]-RYWN (RYLAZE)

Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma (LBL)

Asparaginase Erwinia chrysanthemi [recombinant]-rywn (Rylaze) is considered medically necessary and, therefore, covered for the treatment of ALL and lymphoblastic lymphoma (LBL) in adult and pediatric individuals 1 month or older when all of the following criteria are met:

Asparaginase Erwinia chrysanthemi [recombinant]-rywn (Rylaze) is being used as a component of a multiagent chemotherapeutic regimen
The individual has a history of documented hypersensitivity to E. coli–derived asparaginase (and has fully recovered), OR has silent inactivation
The individual does not have any of the following conditions/contraindications:

History of ≥Grade 3 pancreatitis
History of asparaginase-associated ≥Grade 3 hemorrhagic event or asparaginase-associated thrombus requiring anticoagulation therapy, excluding catheter-related thrombotic events

Non-Hodgkin Lymphoma (NHL)/ Extranodal NK/T-cell lymphoma

Asparaginase Erwinia chrysanthemi [recombinant]-rywn (Rylaze) is considered medically necessary and, therefore, covered for the treatment of extranodal NK/T-cell lymphoma when all of the following criteria are met:

Asparaginase Erwinia chrysanthemi [recombinant]-rywn (Rylaze) is being used as a component of a multi-agent chemotherapeutic regimen
The individual does not have any of the following contraindications:

History of serious hypersensitivity reactions (NCI CTCAE Grades 3 and 4) to asparaginase Erwinia chrysanthemi (Erwinaze), including anaphylaxis
History of serious pancreatitis with prior L-asparaginase therapy manifested by abdominal pain for longer than 72 hours and amylase elevation greater than or equal to 2.0 times the ULN
History of serious thrombosis (e.g., sagittal sinus thrombosis or pulmonary embolism) with prior L-asparaginase therapy
History of serious hemorrhagic events (NCI CTCAE Grade 4 with CNS involvement) with prior L-asparaginase therapy

ADDITIONAL INDICATIONS FOR ERWINASE AND RYLAZE

Asparaginase Erwinia chrysanthemi (Erwinaze)

In accordance with the Centers for Medicare & Medicaid Services (CMS) and in addition to the indications above, asparaginase Erwinia chrysanthemi (Erwinaze) is covered for the following Micromedex Category IIb indications:

Acute myeloid leukemia
Chronic myeloid leukemia
Extranodal NK/T-cell lymphoma, nasal type
Malignant lymphoma

Asparaginase Erwinia chrysanthemi [recombinant]-rywn (Rylaze)

In accordance with the Centers for Medicare & Medicaid Services (CMS) and in addition to the indications above, asparaginase Erwinia chrysanthemi [recombinant]-rywn (Rylaze) is covered for the following Micromedex Category IIb indications:

Acute myeloid leukemia
Chronic myeloid leukemia
Malignant lymphoma

EXPERIMENTAL/INVESTIGATIONAL

All other uses for asparaginase Erwinia chrysanthemi (Erwinaze) and asparaginase Erwinia chrysanthemi [recombinant]-rywn (Rylaze) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

Guidelines

There is no Medicare coverage determination addressing asparaginase Erwinia chrysanthemi (Erwinaze) and asparaginase Erwinia chrysanthemi [recombinant]-rywn (Rylaze); therefore, the Company policy is applicable.

NATIONAL CANCER INSTITUTE COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS

The National Cancer Institute Common Terminology Criteria for Adverse Events describes the severity of adverse events (i.e., organ toxicity) for individuals receiving chemotherapy. Adverse events are evaluated on a Grade Scale of 1-5 with unique clinical descriptions of severity for each adverse event. The general guideline is:

Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated
Grade 2: minimal, local, or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily living (ADL)
Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling, limiting self ADL
Grade 4: life-threatening consequences, urgent intervention indicated
Grade 5: death related to adverse event

For additional information about organ-specific clinical descriptions, refer to https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm.

BENEFIT APPLICATION

Subject to the applicable Evidence of Coverage, asparaginase Erwinia chrysanthemi (Erwinaze) and asparaginase Erwinia chrysanthemi [recombinant]-rywn (Rylaze) are covered under the medical benefits of the Company’s Medicare Advantage products when the medical necessity criteria listed in this medical policy are met.

For Medicare Advantage members, certain drugs are available through either the member's medical benefit (Part B benefit) or pharmacy benefit (Part D benefit), depending on how the drug is prescribed, dispensed, or administered. This medical policy only addresses instances when asparaginase Erwinia chrysanthemi (Erwinaze®) and asparaginase Erwinia chrysanthemi [recombinant]-rywn (Rylaze) are covered under a member's medical benefit (Part B benefit). It does not address instances when asparaginase Erwinia chrysanthemi (Erwinaze®) and asparaginase Erwinia chrysanthemi [recombinant]-rywn (Rylaze) are covered under a member’s pharmacy benefit (Part D benefit).

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Asparaginase Erwinia chrysanthemi (Erwinaze®) was approved by the FDA in November 2011 for the treatment of individuals with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to E. coli–derived asparaginase.

Asparaginase Erwinia chrysanthemi [recombinant]-rywn (Rylaze) was approved by the FDA on June 30, 2021, for the treatment of individuals with ALL and lymphoblastic lymphoma (LBL) in adult and pediatric individuals 1 month or older who have developed hypersensitivity to E. coli–derived asparaginase.

PEDIATRIC

The safety and effectiveness of asparaginase Erwinia chrysanthemi (Erwinaze) have been established in pediatric individuals ages 1 year and older as a component of a multiagent chemotherapeutic regimen for the treatment of patients with ALL who have developed hypersensitivity to E. coli–derived asparaginase.

The safety and effectiveness of asparaginase Erwinia chrysanthemi [recombinant]-rywn (Rylaze) have been established in pediatric individuals ages 1 month and older as a component of a multiagent chemotherapeutic regimen for the treatment of individuals with acute lymphoblastic leukemia (ALL) and LBL who have developed hypersensitivity to E. coli–derived asparaginase.

Description

According to the American Cancer Society, there are approximately 6,590 new cases of acute lymphoblastic leukemia (ALL) occurring in children and adults in the United States. Children younger than 5 years of age have the highest level of risk for developing ALL. ALL, also known as acute lymphocytic leukemia, is a cancer that starts in the white blood cell precursors in the bone marrow and progresses rapidly to spread to other parts of the body.

Treatment for ALL is typically divided into several phases: induction, consolidation, and maintenance. Induction therapy is the initial phase of treatment with the objective of achieving complete remission. Consolidation, or the intensification phase, is a shorter period of chemotherapy to further reduce the amount of leukemic cells and to prevent the development of drug resistance. The individual's level of risk will determine the intensity of the chemotherapy regimen. The maintenance phase helps to prolong the duration of remission.

Asparaginase is commonly used for the treatment of ALL. Leukemic cells lack asparagine synthetase activity, making them unable to synthesize asparagine. They have to depend on an exogenous source of amino acid asparagine for protein metabolism and survival, which is typically part of the regimen for induction therapy. Clinical studies have demonstrated that asparaginase can be used to achieve complete remission for individuals during their first relapse.

ASPARAGINASE ERWINIA CHRYSANTHEMI (ERWINAZE)

In November 2011, asparaginase Erwinia chrysanthemi (Erwinaze) was approved by the US Food and Drug Administration (FDA) as a component of the multiagent chemotherapeutic regimen for the treatment of individuals with ALL who have developed a hypersensitivity to Escherichia coli (E. coli)–derived asparaginase. Erwinia chrysanthemi (Erwinaze) catalyzes the deamidation of asparagine to aspartic acid and ammonia, leading to a reduction of circulating asparagine.

The safety and efficacy of asparaginase Erwinia chrysanthemi (Erwinaze) for intramuscular injection was established in a single-arm multicenter open-label trial. Enrolled in the trial were 58 individuals who were unable to continue to receive pegaspargase due to hypersensitivity reactions. The main outcome measure was the proportion of individuals who achieved a serum trough asparaginase level of greater than or equal to 0.1 IU/mL. A serum trough asparaginase level of greater than or equal to 0.1 IU/mL has been demonstrated to correlate with asparagine depletion and to serum levels that predict clinical efficacy. Individuals received asparaginase Erwinia chrysanthemi (Erwinaze) 25,000 IU/m2 intramuscularly for 2 weeks (total six doses). Greater than 50% of the individuals achieved the prespecified trough asparaginase level at 48 or 72 hours following the third dose.

The safety and efficacy of asparaginase Erwinia chrysanthemi (Erwinaze) for intravenous infusion was studied in an open-label, single-arm, multicenter, pharmacokinetic study. This study enrolled 30 individuals being treated for ALL or lymphoblastic lymphoma (LBL), following an allergy to E. coli asparaginase or pegaspargase. Individuals received asparaginase Erwinia chrysanthemi (Erwinaze), 25,000 IU/m²/dose, intravenously, three days per week for up to 30 weeks. The primary endpoint was determined by the proportion of individuals with a 2-day pre-dose serum asparaginase activity level (48-hour levels taken after the fifth dose) greater than or equal to 0.1 IU/mL in the first 2 weeks of asparaginase Erwinia chrysanthemi (Erwinaze) treatment. The primary endpoint was observed in 83% of individuals.

ASPARAGINASE ERWINIA CHRISANTHEMI [RECOMBINANT]-RYWN (RYLAZE)

On June 30, 2021, asparaginase Erwinia chrysanthemi (recombinant)-rywn (Rylaze) was approved by the FDA for use as a component of a multiagent chemotherapeutic regimen for the treatment of ALL or ABL in pediatric and adult individuals 1 month and older who have developed hypersensitivity to E. coli-derived asparaginase.

Asparaginase Erwinia chrysanthemi (recombinant)-rywn contains an asparagine-specific bacterial enzyme (L-asparaginase). L-asparaginase is a tetrameric enzyme that consists of four identical 35-kDa subunits with a combined molecular weight of 140 kDa. The amino acid sequence is identical to native asparaginase Erwinia chrysanthemi (also known as crisantaspase). The activity of asparaginase Erwinia chrysanthemi (recombinant)-rywn is expressed in units, defined as the amount of enzyme that catalyzes the conversion of 1 μmol of L-asparagine per reaction minute, per mg of protein. Asparaginase Erwinia chrysanthemi (recombinant)-rywn is produced by fermentation of a genetically engineered Pseudomonas fluorescens bacterium containing the DNA that encodes for asparaginase Erwinia chrysanthemi.

The safety of Rylaze was evaluated in a cohort of 33 individuals from the Study JZP458-201 (NCT04145531), who received Rylaze 25 mg/m² intramuscularly on Monday, Wednesday, and Friday for six doses as a replacement for a single dose of pegaspargase as a component of multiagent chemotherapy. The individuals had a median age of 11 years (range, 1–24); the majority of individuals were male (51%) and white (73%). The individuals received a median of four courses of Rylaze (range, 1–14 cycles); 48% of individuals received at least four courses.

The safety and effectiveness of Rylaze in the treatment of ALL and LBL have been established in pediatric individuals 1 month to age less than 17 years who have developed hypersensitivity to a long-acting E. coli–derived asparaginase. The trial included 84 pediatric individuals, including two infants (1 month to <2 years), 62 children (2 years to <12 years old), and 20 adolescents (12 years to <17 years old). The safety and effectiveness of Rylaze have not been established in pediatric individuals younger than 1 month of age. The most frequent serious adverse reactions (in ≥5% of individuals) were febrile neutropenia, dehydration, pyrexia, stomatitis, diarrhea, drug hypersensitivity, infection, nausea, and viral infection. Permanent discontinuation due to an adverse reaction occurred in 9% of individuals who received the Rylaze 25 mg/m² dosage. Adverse reactions resulting in permanent discontinuation included hypersensitivity (6%) and infection (3%).

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

References

American Hospital Formulary Service (AHFS). Drug Information 2023. Asparaginase (Erwinia chrysanthemi) (04/27/20) and Asparaginase Erwinia chrysanthemi (Erwinaze®) (02/17/22). [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed April 18, 2023.

Asparaginase Erwinia chrysanthemi (recombinant)-rywn (Rylaze). Jazz Pharmaceuticals, Inc. 11/18/2022. Available at: http://www.rylaze.com/. Accessed April 18, 2023.

Centers for Medicare & Medicaid Services (CMS). Medicare Benefit Policy Manual.Chapter 15: Covered medical and other health services. 120 - Prosthetic Devices (Rev. 1, 10-01-03). [CMS Web site]. Available at: https://www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/Internet-Only-Manuals-Ioms-Items/Cms012673.html. Accessed April 18, 2023.

ClinicalTrials.gov. An Open-Label Study of JZP-458 (RC-P) in Patients With Acute Lymphoblastic Leukemia (ALL)/Lymphoblastic Lymphoma (LBL). ClinicalTrials.gov Identifier: NCT04145531. First Posted: 10/30/19; Last Update Posted: 08/05/22. Available at: https://clinicaltrials.gov/ct2/show/study/NCT04145531. Accessed April 18, 2023.

Einsiedel H, Stackelberg A, Hartmann R, et. al. Long term outcome in children with relapsed ALL by risk-stratified salvage therapy: results of trial acute lymphoblastic leukemia-relapse study of the Berlin-Frankfurt-Munster Group 87. J Clin Oncol. 2005;23(31):7942-7950.

Elsevier’s Clinical Pharmacology Compendium. Asparaginase (Erwinia chrysanthemi), Asparaginase (Erwinia chrysanthemi [recombinant)-rywn]). [ClinicalKey Web site]. 11/28/2022. Available at: Clinical Pharmacology Home (clinicalkey.com). [via subscription only]. Accessed April 18, 2023.

Keating G. Asparaginase Erwinia chrysanthemi (Erwinase®): A guide to its use in acute lymphoblastic leukemia in the USA. BioDrugs. 2013;27:413-418.

Lexi-Drugs Compendium. Asparaginase (Erwinia). [Lexicomp Online Web site]. 12/15/2022. Available at: http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/3566871 [via subscription only]. Accessed April 18, 2023.

Lexi-Drugs Compendium. Asparaginase (Erwinia [recombinant]). [Lexicomp Online Web site]. 12/15/2022. Available at: http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/7120155?cesid=8aYkOgKcRsU&searchUrl=/lco/action/search?q=rylaze&t=name&acs=false&acq=rylaze [via subscription only]. Accessed April 18, 2023.

National Comprehensive Cancer Network (NCCN). NCCN Guidelines Clinical Practice Guidelines in Oncology: Acute Lymphoblastic Leukemia V1.2022 (04/04/22). [NCCN Web site]. Available at: https://www.nccn.org/professionals/physician_gls/pdf/all.pdf. Accessed April 10, 2023.

National Comprehensive Cancer Network (NCCN). NCCN Guidelines Clinical Practice Guidelines in Oncology: Pediatric Acute Lymphoblastic Leukemia V2.2023 (03/10/2023). [NCCN Web site]. Available at: https://www.nccn.org/professionals/physician_gls/pdf/ped_all.pdf. Accessed April 10, 2023.

National Comprehensive Cancer Network (NCCN). NCCN Guidelines Clinical Practice Guidelines in Oncology: T-Cell Lymphomas Guidelines V1.2023 (01/05/2023). [NCCN Web site]. Available at: https://www.nccn.org/professionals/physician_gls/pdf/ped_all.pdf. Accessed April 10, 2023.

National Comprehensive Cancer Network (NCCN). NCCN Drug and Biologics Compendium. Erwinaze & Rylaze. [National Comprehensive Cancer Network Web site]. 2023. Subscription required. Available at: https://www.nccn.org/professionals/drug_compendium/content/. Accessed April 10, 2023.

Rivera JM, Garcia O, Oriol A, et al. Feasibility and results of subtype-oriented protocols in older adults and fit elderly patients with acute lymphoblastic leukemia: Results of three prospective parallel trials from the PETHEMA group. Leukemia Research. 2016;41:12-20.

Salzer W, Asselin B, Supko JG, et. al. Erwinina asparaginase achieves therapeutic activity after pegaspargase allergy: a report from the Children's Oncology Group. Blood. 2013;122(4):507-514.

Seiter K. Acute lymphoblastic leukemia treatment & management. [Medscape Website]. 04/17/2023. Available at: http://emedicine.medscape.com/article/207631-treatment. Accessed April 18, 2023.

Truven Health Analytics. Micromedex® Healthcare Series. DrugDex®. Asparaginase & Asparaginase (recombinant)-rywn. [Micromedex Web site]. Last modified 03/07/2023. Available at: https://www.micromedexsolutions.com/micromedex2/librarian/ssl/true [via subscription only]. Accessed April 18, 2023.

US Department of Health and Human Services. Common terminology criteria for adverse events (CTCTAE). V5.0. 09/21/2020. Available at: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm. Accessed April 18, 2023.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs@FDA. Approval letter & Prescribing information. Asparaginase Erwinia chrysanthemi (Erwinaze®). [FDA Web site]. 12/2019. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed June 22, 2022.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Approval letter & Prescribing information. Asparaginase (Erwinia chrysanthemi [recombinant)-rywn]) (Rylaze) . [FDA Web site]. 11/18/2022. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed April 18, 2023.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

ERWINAZE IS MEDICALLY NECESSARY WHEN REPORTED WITH THE FOLLOWING DIAGNOSIS CODES

C83.50 Lymphoblastic (diffuse) lymphoma, unspecified site
C83.51 Lymphoblastic (diffuse) lymphoma, lymph nodes of head, face, and neck
C83.52 Lymphoblastic (diffuse) lymphoma, intrathoracic lymph nodes
C83.53 Lymphoblastic (diffuse) lymphoma, intra-abdominal lymph nodes
C83.54 Lymphoblastic (diffuse) lymphoma, lymph nodes of axilla and upper limb
C83.55 Lymphoblastic (diffuse) lymphoma, lymph nodes of inguinal region and lower limb
C83.56 Lymphoblastic (diffuse) lymphoma, intrapelvic lymph nodes
C83.57 Lymphoblastic (diffuse) lymphoma, spleen
C83.58 Lymphoblastic (diffuse) lymphoma, lymph nodes of multiple sites
C83.59 Lymphoblastic (diffuse) lymphoma, extranodal and solid organ site

C86.0 Extranodal NK/T-cell lymphoma, nasal type
C91.00 Acute lymphoblastic leukemia not having achieved remission
C91.01 Acute lymphoblastic leukemia, in remission
C91.02 Acute lymphoblastic leukemia, in relapse
C92.00 Acute myeloblastic leukemia, not having achieved remission
C92.01 Acute myeloblastic leukemia, in remission
C92.02 Acute myeloblastic leukemia, in relapse
C92.10 Chronic myeloid leukemia, BCR/ABL-positive, not having achieved remission
C92.11 Chronic myeloid leukemia, BCR/ABL-positive, in remission
C92.12 Chronic myeloid leukemia, BCR/ABL-positive, in relapse

RYLAZE IS MEDICALLY NECESSARY WHEN REPORTED WITH THE FOLLOWING DIAGNOSIS CODES

C84.90 Mature T/NK-cell lymphomas, unspecified, unspecified site

C84.91 Mature T/NK-cell lymphomas, unspecified, lymph nodes of head, face, and neck

C84.92 Mature T/NK-cell lymphomas, unspecified, intrathoracic lymph nodes

C84.93 Mature T/Nk-cell lymphomas, unspecified, intra-abdominal lymph nodes

C84.94 Mature T/NK-cell lymphomas, unspecified, lymph nodes of axilla and upper limb

C84.95 Mature T/NK-cell lymphomas, unspecified, lymph nodes of inguinal region and lower limb

C84.96 Mature T/NK-cell lymphomas, unspecified, intrapelvic lymph nodes

C84.97 Mature T/NK-cell lymphomas, unspecified, spleen

C84.98 Mature T/NK-cell lymphomas, unspecified, lymph nodes of multiple sites

C84.99 Mature T/NK-cell lymphomas, unspecified, extranodal and solid organ sites

C84.Z0 Other mature T/NK-cell lymphomas, unspecified site

C84.Z1 Other mature T/NK-cell lymphomas, lymph nodes of head, face, and neck

C84.Z2 Other mature T/NK-cell lymphomas, intrathoracic lymph nodes

C84.Z3 Other mature T/NK-cell lymphomas, intra-abdominal lymph nodes

C84.Z4 Other mature T/NK-cell lymphomas, lymph nodes of axilla and upper limb

C84.Z5 Other mature T/NK-cell lymphomas, lymph nodes of inguinal region and lower limb

C84.Z6 Other mature T/NK-cell lymphomas, intrapelvic lymph nodes

C84.Z7 Other mature T/NK-cell lymphomas, spleen

C84.Z8 Other mature T/NK-cell lymphomas, lymph nodes of multiple sites

C84.Z9 Other mature T/NK-cell lymphomas, extranodal and solid organ sites

HCPCS Level II Code Number(s)

J9019

Injection, asparaginase (Erwinaze), 1,000 IU

J9021

Injection, asparaginase, recombinant, (Rylaze), 0.1 mg

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Revisions From MA08.085g:

06/19/2023

This version of the policy will become effective 06/19/2023.

This policy was updated to communicate the Company's coverage position for Erwinaze and Rylaze, in alignment with the National Comprehensive Cancer Network (NCCN) and the Centers for Medicare & Medicaid Services (CMS) requirements for Micromedex Drug Compendia (Category IIb indications).

The NCCN recommends Rylaze for the treatment of extranodal NK/T-cell lymphoma (all types).

The NCCN recommends Rylaze for the treatment of relapsed ALL or LBL, so the criteria that "The individual does not have any of the following conditions/contraindications: relapsed ALL or LBL" was removed.

The following ICD-10 CM codes have been added to this policy for Rylaze:

C84.90 Mature T/NK-cell lymphomas, unspecified, unspecified site

C84.91 Mature T/NK-cell lymphomas, unspecified, lymph nodes of head, face, and neck

C84.92 Mature T/NK-cell lymphomas, unspecified, intrathoracic lymph nodes

C84.93 Mature T/Nk-cell lymphomas, unspecified, intra-abdominal lymph nodes

C84.94 Mature T/NK-cell lymphomas, unspecified, lymph nodes of axilla and upper limb

C84.95 Mature T/NK-cell lymphomas, unspecified, lymph nodes of inguinal region and lower limb

C84.96 Mature T/NK-cell lymphomas, unspecified, intrapelvic lymph nodes

C84.97 Mature T/NK-cell lymphomas, unspecified, spleen

C84.98 Mature T/NK-cell lymphomas, unspecified, lymph nodes of multiple sites

C84.99 Mature T/NK-cell lymphomas, unspecified, extranodal and solid organ sites

C84.Z0 Other mature T/NK-cell lymphomas, unspecified site

C84.Z1 Other mature T/NK-cell lymphomas, lymph nodes of head, face, and neck

C84.Z2 Other mature T/NK-cell lymphomas, intrathoracic lymph nodes

C84.Z3 Other mature T/NK-cell lymphomas, intra-abdominal lymph nodes

C84.Z4 Other mature T/NK-cell lymphomas, lymph nodes of axilla and upper limb

C84.Z5 Other mature T/NK-cell lymphomas, lymph nodes of inguinal region and lower limb

C84.Z6 Other mature T/NK-cell lymphomas, intrapelvic lymph nodes

C84.Z7 Other mature T/NK-cell lymphomas, spleen

C84.Z8 Other mature T/NK-cell lymphomas, lymph nodes of multiple sites

C84.Z9 Other mature T/NK-cell lymphomas, extranodal and solid organ sites

Revisions From MA08.085f:

08/15/2022

This version of the policy will become effective 08/15/2022.

This policy was updated to communicate the Company's coverage position for Erwinaze and Rylaze, in alignment with National Comprehensive Cancer Network (NCCN) and the clinical study criteria.

Erwinaze induction therapy for Acute Lymphoblastic Leukemia (ALL) now includes individuals with substantial comorbities.
Erwinaze information for ALL was updated regarding use with tyrosine kinase inhibitors (TKI).
Rylaze coverage criteria was clarified for ALL and LBL, in accordance with the clinical study criteria.
Rylaze is covered for Acute myeloid leukemia, Chronic myeloid leukemia, and Malignant lymphoma, in accordance with the Centers for Medicare and Medicaid Services (CMS) requiremens for Micromedex Drug Compendia (Category IIb indications).

Revisions From MA08.085e:

01/01/2022

This policy has been identified for the HCPCS code update, effective 01/01/2022.
The following HCPCS codes have been termed from this policy:

C9399 Unclassified drugs or biologics
J3590 Unclassified biologics

The following HCPCS code has been added to this policy:

J9021 Injection, asparaginase, recombinant, (rylaze), 0.1 mg

Revisions From MA08.085d:

09/13/2021

This version of the policy will become effective 09/13/2021

The policy has been updated to communicate changes based on National Comprehensive Cancer Network (NCCN) and Micromedex Drugdex compendia. Criteria have been revised for Erwinase® for the treatment of Acute Lymphoblastic Leukemia (ALL). New drug asparaginase erwinia chrysanthemi [recombinant]-rywn (Rylaze™) and indications were added for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric individuals

The following ICD-10 CM codes have been added to this policy:

C83.50 Lymphoblastic (diffuse) lymphoma, unspecified site

C83.51 Lymphoblastic (diffuse) lymphoma, lymph nodes of head, face, and neck

C83.52 Lymphoblastic (diffuse) lymphoma, intrathoracic lymph nodes

C83.53 Lymphoblastic (diffuse) lymphoma, intra-abdominal lymph nodes

C83.54 Lymphoblastic (diffuse) lymphoma, lymph nodes of axilla and upper limb

C83.55 Lymphoblastic (diffuse) lymphoma, lymph nodes of inguinal region and lower limb

C83.56 Lymphoblastic (diffuse) lymphoma, intrapelvic lymph nodes

C83.57 Lymphoblastic (diffuse) lymphoma, spleen

C83.58 Lymphoblastic (diffuse) lymphoma, lymph nodes of multiple sites

C83.59 Lymphoblastic (diffuse) lymphoma, extranodal and solid organ sites

Revisions From MA08.085c:

01/18/2021

The policy has been updated to communicate changes based on National Comprehensive Cancer Network (NCCN) and Micromedex Drugdex compendia. Criteria have been revised to include use of Erwinase® as a component of a multi-agent chemotherapeutic regimen for the treatment of extranodal NK/T-cell lymphoma, nasal type. Medical Necessity coverage was added for the following oncologic conditions, in accordance with the Centers for Medicare and Medicaid Services (CMS) and Micromedex Drugdex compendia (Category IIb indications)

Acute myeloid leukemia
Chronic myeloid leukemia
Malignant lymphoma

The following ICD-10 CM codes have been added to this policy:

C85.80 Other specified types of non-Hodgkin lymphoma, unspecified site

C85.81 Other specified types of non-Hodgkin lymphoma, lymph nodes of head, face, and neck

C85.82 Other specified types of non-Hodgkin lymphoma, intrathoracic lymph nodes

C85.83 Other specified types of non-Hodgkin lymphoma, intra-abdominal lymph nodes

C85.84 Other specified types of non-Hodgkin lymphoma, lymph nodes of axilla and upper limb

C85.85 Other specified types of non-Hodgkin lymphoma, lymph nodes of inguinal region and lower limb

C85.86 Other specified types of non-Hodgkin lymphoma, intrapelvic lymph nodes

C85.87 Other specified types of non-Hodgkin lymphoma, spleen

C85.88 Other specified types of non-Hodgkin lymphoma, lymph nodes of multiple sites

C85.89 Other specified types of non-Hodgkin lymphoma, extranodal and solid organ sites

C86.0 Extranodal NK/T-cell lymphoma, nasal type

C91.01 Acute lymphoblastic leukemia, in remission

C92.00 Acute myeloblastic leukemia, not having achieved remission

C92.01 Acute myeloblastic leukemia, in remission

C92.02 Acute myeloblastic leukemia, in relapse

C92.10 Chronic myeloid leukemia, BCR/ABL-positive, not having achieved remission

C92.11 Chronic myeloid leukemia, BCR/ABL-positive, in remission

C92.12 Chronic myeloid leukemia, BCR/ABL-positive, in relapse

Revisions From MA08.085b:

12/16/2019

This version of the policy will become effective 12/16/2019.

The policy has been updated to communicate changes based on National Comprehensive Cancer Network (NCCN). Criteria have been revised to include use of Erwinase® as first-line therapy for adult individuals over 65 years of age and used in pediatric individuals with acute lymphoblastic leukemia.

Revisions From MA08.085a:

11/19/2018.

This version of the policy will become effective 11/19/2018.

The policy has been updated to communicate changes based on National Comprehensive Cancer Network (NCCN).Criteria have been revised to include hypersensitivity to Oncaspar.

Revisions From MA08.085:

04/11/2018	This policy has been reissued in accordance with the Company's annual Policy Confirmation Review track. The references were updated accordingly. The policy was updated to be consistent with current template wording and format. The adoptable source for this policy is FDA labeling (03/2016), Micromedex (11/2016), and AHFS (02/2018), NCCN compendium (03/2018), NCCN Acute Lymphoblastic Leukemia Guidelines V1.2018 (03/2018).
06/07/2017	This policy has been reissued in accordance with the Company's annual review process.
01/01/2017	The following new policy has been developed to communicate of the Company’s coverage criteria for asparaginase Erwinia chrysanthemi (Erwinaze®).

Version Effective Date:

6/19/2023

Version Issued Date:

6/19/2023

Version Reissued Date: