Asparlas (calaspargase pegol-mknl) was FDA approved in December 2018. The FDA approval of Asparlas (calaspargase pegol-mknl) was based on a demonstration of the achievement and maintenance of nadir serum asparaginase activity (NSAA) above the level of 0.1 U/mL using Asparlas (calaspargase pegol-mknl) 2500 U/m² intravenously every 3 weeks. The pharmacokinetics of Asparlas (calaspargase pegol-mknl) were studied when used in combination with multiagent chemotherapy in 124 patients with B cell lineage acute lymphoblastic leukemia (ALL). Chemotherapeutic agents used in the study include doxorubicin hydrochloride, cytarabine, prednisone, methotrexate, cyclophosphamide, mercaptopurine, dexamethasone, thioguanine, daunorubicin hydrochloride, and vincristine sulfate. The results showed that 123 (99%) of the 124 patients maintained NSAA > 0.1 U/mL at 6, 12, 18, 24 and 30 weeks.

Asparlas (calaspargase pegol-mknl) may cause serious and life threatening allergic reactions and blood clots. Other serious side effects include inflammation in the pancreas and liver damage.

Policy:
NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.

The requirements of the Horizon BCBSNJ Erwinaze (Asparaginase Erwinia Chrysanthemi), Oncaspar (pegaspargase), and Asparlas (calaspargase pegol-mknl) Program may require a precertification/prior authorization via MagellanRx Management. These requirements are member-specific: please verify member eligibility and requirements through the Horizon Provider Portal (www.horizonblue.com/provider). Ordering clinicians should request pre-certification from MagellanRx Management at ih.magellanrx.com or call 1-800-424-4508 (when applicable).

I. Asparaginase E. chrysanthemi (Erwinaze^TM) is considered medically necessary if the patient meets the following criteria:

• The prescriber is a specialist in the area of the patient’s diagnosis (e.g. oncologist, hematologist) or has consulted with a specialist in the area of the patient’s diagnosis AND
• Member is 1 year of age or older AND
• Diagnosis of acute lymphoblastic leukemia (ALL) AND
• Used as a component of a multi-agent chemotherapeutic regimen AND
• Has a history of hypersensitivity (documented Grade 2 – 4 hypersensitivity) to E. coli-derived asparaginase (Oncaspar®) AND
• No history of serious pancreatitis with prior L-asparaginase therapy AND
• No history of serious thrombosis with prior L-asparaginase therapy AND
• No history of serious hemorrhagic events with prior L-asparaginase therapy

A. Prior to starting therapy with Oncaspar, the following must be documented:
• No history of serious thrombosis, pancreatitis, or serous hemorrhagic events with prior L-asparaginase therapy AND
• No severe hepatic impairment AND
• The prescriber is a specialist in the area of the patient’s diagnosis (e.g. oncologist, hematologist) or has consulted with a specialist in the area of the patient’s diagnosis
B. For the treatment of Acute Lymphoblastic Leukemia
• Member is 1 year of age and older AND
• Must be use as a component of multi-agent chemotherapy AND
• White blood cell count < 50,000/uL and
• Surface immunoglobulin (IG) positive leukemic blasts < 20% AND
• One of the following:
  · Used as first line therapy OR
  · Used to treat patients with a hypersensitivity to native forms of L-asparaginase
[INFORMATIONAL NOTES:
Documented hypersensitivity reactions are based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). Grade refers to the severity of the adverse events. Grade 2 is moderate (minimal, local, or noninvasive intervention indicated); Grade 3 is severe or medically significant but not life-threatening (hospitalization or prolongation of hospitalization indicated); Grade 4 is life-threatening consequences (urgent intervention indicated). Examples of Grade 2-4 hypersensitivity reactions include:
· Allergic reaction:
o Grade 2: Intervention or infusion interruption indicated; responds promptly to symptomatic treatment (e.g., antihistamines, NSAIDS, narcotics); prophylactic medications indicated for <24 hrs
o Grade 3: Prolonged (e.g., not rapidly responsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae (e.g., renal impairment, pulmonary infiltrates)
o Grade 4: Life-threatening consequences; urgent intervention indicated
· Anaphylaxis:
o Grade 3: Symptomatic bronchospasm, with or without urticaria; parenteral intervention indicated; allergy-related edema/angioedema; hypotension
o Grade 4: Life-threatening consequences; urgent intervention indicated

The NCCN guidelines for ALL recommends the use of Oncaspar in the treatment of patients with ALL. For patients who develop a severe hypersensitivity reaction during treatment with Oncaspar, Erwinaze should be substituted. The NCCN compendia recommends the use of Oncaspar for treatment ALL meeting the following conditions:

· Acute Lymphoblastic Leukemia
• For Philadelphia chromosome-positive ALL in AYA patients as a component of
  • COG AALL-0031 regimen (vincristine, prednisone or dexamethasone, and pegaspargase, with or without daunorubicin; or prednisone or dexamethasone and pegaspargase with or without daunorubicin; imatinib added during consolidation blocks) for induction/consolidation therapy
  • COG AALL-0031 regimen + TKI (bosutinib, dasatinib, imatinib, nilotinib, ponatinib) for relapsed/refractory disease (if not used for induction)
• Induction/consolidation therapy for Philadelphia chromosome-negative ALL in AYA patients as a component of
  • CALGB 10403 regimen (daunorubicin, vincristine, prednisone, and pegaspargase) (patients aged <40 years)
  • COG AALL0232 regimen (daunorubicin, vincristine, prednisone, and pegaspargase) (patients aged ≤21 years)
  • COG AALL0434 regimen (daunorubicin, vincristine, prednisone, and pegaspargase; nelarabine added to consolidation) (for T-ALL)
  • DFCI ALL regimen based on DFCI Protocol 00-01 (doxorubicin, vincristine, prednisone, high-dose methotrexate, and pegaspargase) (patients aged <50 years)
  • GRAALL-2005 regimen (daunorubicin, vincristine, prednisone, pegaspargase, and cyclophosphamide) with rituximab for CD20-positive disease (patients aged < 60 years)
  • PETHEMA ALL-96 regimen (daunorubicin, vincristine, prednisone, pegaspargase, and cyclophosphamide) (patients aged <30 years)
  • USC ALL based on CCG-1882 regimen (daunorubicin, vincristine, prednisone, and methotrexate with augmented pegaspargase) (patients aged 18-57 years)
  • Linker 4-drug regimen (daunorubicin, vincristine, prednisone, pegaspargase)
• Induction/consolidation therapy for Philadelphia chromosome-negative ALL in adult patients as a component of
  • CALGB 8811 Larson regimen (daunorubicin, vincristine, prednisone, pegaspargase, and cyclophosphamide)
  • GRAALL-2005 regimen (daunorubicin, vincristine, prednisone, pegaspargase, and cyclophosphamide) with rituximab for CD20-positive disease (patients aged <60 years)
  • Linker 4-drug regimen (daunorubicin, vincristine, prednisone, and pegaspargase)
  • MRC UKALLXII/ECOG2993 regimen (daunorubicin, vincristine, prednisone, and pegaspargase) (induction phase I)
• Induction therapy for Philadelphia chromosome-negative ALL in adults aged ≥65 years as a component of CALGB 9111 regimen (cyclophosphamide, daunorubicin, vincristine, prednisone, and pegaspargase) (high intensity)
• Therapy for relapsed/refractory Philadelphia chromosome-negative ALL or for relapsed/refractory Philadelphia chromosome-positive ALL refractory to TKIs as a component of
  • augmented Hyper-CVAD (hyper-fractionated cyclophosphamide, intensified vincristine, doxorubicin, intensified dexamethasone, and pegaspargase, alternating with high-dose methotrexate and cytarabine)
  • MOpAD regimen (methotrexate, vincristine, pegaspargase, dexamethasone) with rituximab for CD20-positive disease
• Central nervous system directed therapy as systemic chemotherapy]

For Oncaspar chemotherapeutic regimens used in the clinical studies were as follows:

Agent	Timing
Induction
Vincristine IV	1.5 mg/m2 days 0, 7, 14, 21
Prednisone PO	40 mg/m2 days 0-28 then 10 day taper
Pegaspargase IM	2500 IU/m2 day 3
native asparaginase IM	6000 IU/m2 days 3, 5, 8, 10, 12, 15, 17, 19, 22
Cytarabine IT	30 mg, 50 mg, or 70 mg day 0*
Methotrexate IT	8 mg, 10 mg, or 12 mg days 7, 28*
Consolidation
Vincristine IV	1.5 mg/m2 days 0, 28, 56
6-mercatopurine PO	75 mg/m2 days 1-28
Methotrexate IT	8 mg, 10 mg, or 12 mg days 7, 14, 21*
Interim maintenance no.1 and no. 2
Vincristine IV	1.5 mg/m2 days 0, 7, 14
Dexamethasone PO	10 mg/m2 days 0-6, 14-20
Pegaspargase IM	2500 IU/m2 day 3
Native asparaginase IM	6000 IU/m2 days 3, 5, 8, 10, 12, 15
Doxorubicin IV	25 mg/m2 days 0, 7, 14
Methotrexate IT	8 mg, 10 mg, or 12 mg days 0, 28, 35*
Cyclophosphamide IV	1000 mg/m2 day 28
Cytarabine IV or SC	75 mg/m2 days 29-32, 36-39
Thioguanine PO	60 mg/m2 days 28-41
Maintenance
Vincristine IV	60 mg/m2 days 28-41
Prednisone PO	40 mg/m2 days 0-4 every 4 weeks
Methotrexate PO	20 mg/m2 weekly
6-mercaptopurine PO	75 mg/m2 daily
Methotrexate IT	8 mg, 10 mg, or 12 mg every 3 months*

*The dose of IT medications was based on age

A. Prior to starting therapy with Asparlas, the following must be documented:
• No history of serious thrombosis, pancreatitis, hemorrhagic events or serious hypersensitivity reactions with prior L-asparaginase therapy AND
• No severe hepatic impairment AND
• The prescriber is a specialist in the area of the patient’s diagnosis (e.g. oncologist, hematologist) or has consulted with a specialist in the area of the patient’s diagnosis AND
B. For the treatment of Acute Lymphoblastic Leukemia (ALL)
• Member is 1 month to 21 years of age AND
• Must be use as a component of multi-agent chemotherapy AND
• Member has not have had any prior cytotoxic chemotherapy with the exception of steroids and intrathecal cytarabine AND
• Member does not have Down syndrome AND
• If the member is a post-menarchal female, pregnancy test with a negative result must be obtained AND
• If the member is a male, member does not have testicular leukemia at diagnosis

• To substitute for a dose of pegaspargase (Oncaspar®):
  • 25,000 IU/m² administered intramuscularly or intravenously three times a week (Monday/Wednesday/Friday) for six doses for each planned dose of pegaspargase.
• To substitute for a dose of native E. coli asparaginase (Elspar®):
  • 25,000 IU/m² administered intramuscularly or intravenously for each scheduled dose of native E. coli asparaginase within a treatment
• For intramuscular injections, do not exceed 2 mL per injection site.

The safety and efficacy of intravenous administration were determined in Study 2 by characterizing the PK of a 25,000 IU/m² Erwinaze dose given 3 days per week on a Monday, Wednesday, and Friday schedule for up to 30 weeks. This open-label, single-arm, multicenter PK study enrolled 30 patients. The main outcome measure was determination of the proportion of patients with 2-day NSAA levels (48-hour levels taken after the fifth dose) ≥ 0.1 IU/mL in the first 2 weeks of Erwinaze treatment. The main study objective was met with an asparaginase activity level of ≥ 0.1 IU/mL 48 hours after the fifth dose observed in 83% of patients. The 72-hour post dose 6 asparaginase activity level of ≥ 0.1 IU/mL was the secondary endpoint, with 43% of patients achieving this endpoint.]

· 21 years of age and younger: Inject 2,500 IU/m² intramuscularly or intravenously no more frequently than every 14 days.
· Older than 21 years of age: Inject 2,000 IU/m² intramuscularly or intravenously no more frequently than every 14 days.

· Inject 2,500 IU/m² intravenously no more frequently than every 21 days

• Member continues to meet the initial approval criteria AND
• Member has stabilization of disease and/or absence of disease progression AND
• Absence of unacceptable toxicity from the drug (e.g., severe hypersensitivity reactions including anaphylaxis, hyperglycemia, pancreatitis, thrombosis, bleeding, etc.)

• Member continues to meet the initial approval criteria AND
• Stabilization of disease and/or absence of progression of disease AND
• Absence of unacceptable toxicity from the drug (e.g., allergic reactions (including anaphylaxis), central nervous system (CNS) thrombosis, coagulopathy, elevated transaminases, hyperbilirubinemia, hyperglycemia, and pancreatitis, etc.)

• Member continues to meet the initial approval criteria AND
• Member has stabilization of disease and/or absence of disease progression AND
• There is absence of unacceptable toxicity from the drug (e.g. allergic reactions (including anaphylaxis), central nervous system (CNS) thrombosis, coagulopathy, elevated transaminases, hyperbilirubinemia, hyperglycemia, and pancreatitis, etc.)

There is no National Coverage Determination (NCD). In the absence of an NCD, coverage decisions are left to the discretion of Local Medicare Carriers. Novitas Solutions, Inc, the Local Medicare Carrier for jurisdiction JL, has not issued a determination for this service. Therefore, Medicare Advantage Products will follow the Horizon Policy.

Medicaid Coverage

For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf

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Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

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Index:
Erwinaze (Asparaginase Erwinia Chrysanthemi)
Asparaginase Erwinia Chrysanthemi (Erwinaze)
Oncaspar (pegaspargase)
Pegaspargase (Oncaspar)
Asparlas (calaspargase pegol-mknl)
Calaspargase pegol-mknl (Asparlas)

References:

1. Erwinaze^TM (asparaginase Erwinia chrysanthemi) Prescribing Information. EUSA Pharma. Langhorne, PA. 2016

2. Erwinaze™ (asparaginase Erwinia chrysanthemi) AMCP-format Dossier. EUSA Pharma. Langhorne, PA. November 2011.

3. Curtis RE, Freedman DM, Ron E, et al (eds). New Malignancies Among Cancer Survivors: SEER Cancer Registries, 1973-2000. National Cancer Institute, NIH Publ. No. 05-5302. Bethesda, MD, 2006.

4. National Comprehensive Cancer Network – Drugs & Biologics Compendium. Asparaginase Erwinia chrysanthemi. Available at: http://www.nccn.org/professionals/drug_compendium/MatrixGenerator
/Matrix.aspx?AID=396. Accessed on February 25, 2014.

5. Asparaginase (Erwinia chrysanthemi). In: McEvoy GK, editor. AHFS: Drug Information (2015). Bethesda, MD: American Society of Health-System Pharmacists; 2015. Updated October 30, 2012.

Accessed March 09, 2015. http://online.statref.com/Document.aspx?fxId=1&docId=237

      /Matrix.aspx?AID=396. Accessed April 2019.

17. Clinicaltrials.gov. SC-PEG Asparaginase vs. Oncaspar in Pediatric Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma. NCT01574274. Accessed August 2019. Available at: https://clinicaltrials.gov/ct2/show/NCT01574274

Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

HCPCS

J9266
J9019
J9118