Pegaspargase (Oncaspar), Asparaginase Erwinia Chrysanthemi (Erwinaze), and Calaspargase Pegol-mknl (Asparlas)

Section: Injections
Effective Date: February 01, 2020
Revised Date: January 27, 2020
Last Reviewed: January 22, 2020

Description

Pegaspargase (Oncaspar®) is an asparagine specific enzyme that catalyzes the conversion of the amino acid L-asparagine into aspartic acid and ammonia.

Asparaginase Erwinia Chrysanthemi (Erwinaze®) is an asparagine specific enzyme that catalyzes the conversion of the amino acid L-asparagine into aspartic acid and ammonia indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of individuals who have developed hypersensitivity to E. coli-derived asparaginase.

Calaspargase pegol-mknl (AsparlasTM) is an asparagine specific enzyme that catalyzes the conversion of the amino acid L-asparagine into aspartic acid and ammonia. The pharmacological effect is thought to be based on selective killing of leukemic cells due to depletion of plasma L-asparagine. Leukemic cells with low expression of asparagine synthetase have a reduced ability to synthesize L-asparagine, and therefore depend on an exogenous source of L-asparagine for survival. 

Criteria

Coverage is subject to the specific terms of the member’s benefit plan.

Federal Employee Program members (FEP) should check with their Retail Pharmacy Program to determine if prior approval is required by calling the Retail Pharmacy Program at 1-800-624-5060 (TTY: 1-800-624-5077). FEP members can also obtain the list through the www.fepblue.org website.

Pegaspargase (Oncaspar) may be considered medically necessary when any of the following criteria are met:

Food and Drug Administration (FDA) Indications

Acute Lymphoblastic Leukemia, ALL

  • As a component of a multiagent chemotherapeutic regimen for the first-line treatment of pediatric and adult individuals with acute lymphoblastic leukemia (ALL); or
  • As a component of a multiagent chemotherapeutic regimen for the treatment of pediatric and adult individuals with ALL and hypersensitivity to native forms of L-asparaginase; or

 

National Comprehensive Cancer Network (NCCN) Indications

Acute Lymphoblastic Leukemia, ALL, Pediatric

  • Induction therapy for ANY of the following pediatric acute lymphoblastic leukemia’s as a component of:
    • COG AALL0932 regimen, based on COG AALL0331 regimen (SR arm) for Ph-negative B-ALL (SR arm: dexamethasone, vincristine, pegaspargase; intrathecal (IT) therapy: cytarabine then methotrexate); or
    • COG AALL1131 regimen, based on COG AALL0232 regimen (HR arm) for Ph-negative B-ALL (HR arm: prednisone or dexamethasone, vincristine, pegaspargase, daunorubicin; IT therapy: cytarabine then methotrexate); or
    • DFCI ALL Protocol 05-001 (prednisone, vincristine, pegaspargase, doxorubicin, IT cytarabine then triple IT (ITT) therapy with methotrexate, cytarabine, corticosteroid) for Ph-negative B-ALL; or
    • DFCI ALL Protocol 16-001, based on DFCI ALL Protocol 05-001 (dexamethasone, vincristine, pegaspargase, doxorubicin) for Ph-negative B-ALL; or
    • Total Therapy XVI regimen, based on Total Therapy XV regimen (prednisone, vincristine, daunorubicin, pegaspargase, cyclophosphamide, cytarabine, 6-mercaptopurine (6-mp), ITT) for Ph-negative B-ALL; or
    • Total Therapy XVII regimen, based on Total Therapy XV regimen (prednisone, vincristine, daunorubicin, pegaspargase, cyclophosphamide, cytarabine, 6-mercaptopurine (6-mp), ITT) for Ph-negative B-ALL; or
    • COG AALL1131 regimen + dasatinib (vincristine, dexamethasone,or prednisone, daunorubicin, pegaspargase; IT therapy: cytarabine then methotrexate) for Ph-like B-ALL; or
    • DFCI ALL Protocol 16-001 (VHR arm) + dasatinib (dexamethasone, vincristine, pegaspargase, doxorubicin, cyclophosphamide, etoposide, high-dose cytarabine, pegasparase, doxorubicin + dasatinib, IT therapy: methotrexate) for Ph-like B-ALL with ABL class kinase fusion; or
    • Total Therapy XVII regimen + dasatinib (prednisone, vincristine, daunorubicin, pegaspargase, cyclophosphamide, cytarabine, 6-MP, ITT, dasatinib) for Ph-like B-ALL with ABL class kinase fusion; or
    • Total Therapy XVII regimen + ruxolitinib (prednisone, vincristine, daunorubicin, pegaspargase, cyclophosphamide, cytarabine, 6-MP, ITT, ruxolitinib) for Ph-like B-ALL with mutations associated with JAK-STAT pathway activation; or
    • COG AALL0031 regimen + imatinib (vincristine, asparinase, prednisone/dexamethasone with or without daunorubicin) for Ph-positive B-ALL; or
    • COG AALL0622 regimen + dasatinib (prednisone or dexamethasone, vincristine, pegaspargase, daunorubicin or doxorubicin; IT therapy: methotrexate, hydrocortisone, cytarabine) for Ph-positive B-ALL; or
    • Total Therapy XVII regimen + dasatinib (prednisone, vincristine, daunorubicin, pegaspargase, cyclophosphamide, cytarabine, 6-MP, ITT, dasatinib) for Ph-positive B-ALL; or
    • COG AALL1231 regimen (dexamethasone, vincristine, pegaspargase, daunorubicin) for T-ALL; or
    • COG AALL0434 (prednisone, vincristine, pegaspargase, daunorubicin) regimen for T-ALL; or
    • DFCI ALL Protocol 16-001, based on DFCI ALL Protocol 05-001 (dexamethasone, vincristine, pegaspargase, doxorubicin) for T-ALL; or
    • SJCRH regimen, based on Total Therapy XVII Protocol (prednisone, vincristine, pegaspargase, cyclophosphamide, daunorubicin, 6-MP, cytarabine) for T-ALL; or
    • Interfant regimens [prednisone, dexamethasone, vincristine, cytarabine, daunorubicin, pegaspargase, methotrexate; IT therapy: cytarabine, prednisone (if initial CNS involvement, methotrexate, prednisone)] for infant ALL; or
  • Consolidation therapy for ANY of the following pediatric acute lymphoblastic leukemia’s as a component of:
    • COG AALL0932 regimen, based on COG AALL0331 regimen (SR-Avg/High arm) (cyclophosphamide, cytarabine, 6-MP, vincristine, pegaspargase, IT therapy: methotrexate) for Ph-negative B-ALL; or
    • COG AALL1131 regimen, based on COG AALL0232 regimen (HR arm) (cyclophosphamide, cytarabine, 6-MP, vincristine, pegaspargase; IT therapy: methotrexate) for Ph-negative B-ALL; or
    • DFCI ALL Protocol 05-001 (SR arm or HR/VHR arms) (SR arm: high-dose methotrexate, vincristine, pegasparagase, 6-MP, dexamethasone; IT therapy: methotrexate or ITT or HR/VHR arms: high-dose methotrexate, vincristine, pegasparagase, 6-MP, dexamethasone, doxorubicin, dexrazoxane; IT therapy: methotrexate or ITT) for Ph-negative B-ALL; or
    • DFCI ALL Protocol 16-001, based on DFCI ALL Protocol 05-001 (SR arm or HR/VHR arms) (SR arm: high-dose methotrexate, vincristine, pegasparagase, 6-MP, examethasone; IT therapy: methotrexate or ITT or HR/VHR arms: high-dose methotrexate, vincristine, pegasparagase, 6-MP, dexamethasone, doxorubicin, dexrazoxane; IT therapy: methotrexate or ITT) for Ph-negative B-ALL; or
    • COG AALL1131 regimen + dasatinib (cyclophosphamide, cytarabine, 6-MP, vincristine,pegaspargase, plus dasatinib; IT therapy: methotrexate) for Ph-like B-ALL and CRLF2- with ABL class kinase fusion; or
    • COG AALL1521 regimen + ruxolitinib (cyclophosphamide, cytarabine, 6-MP, vincristine, pegaspargase, plus ruxolitinib, IT therapy: methotrexate) for Ph-like B-ALL and CRLF2+ or CRLF2- with JAK2 fusions, EPOR rearrangements, SH2B3 alterations, IL7R insertions/deletions; or
    • DFCI ALL Protocol 16-001 + dasatinib (high-dose methotrexate, 6-MP, dexamethasone, vincristine, cyclophosphamide, etoposide, high-dose cytarabine, pegaspargase, doxorubicin plus dasatinib, IT therapy: methotrexate) for Ph-like B-ALL with ABL class kinase fusion; or
    • EsPhALL regimen (COG AALL1122 or SR arm of COG AALL1631) + imatinib or dasatinib and an HR backbone of the Berlin-Frankfurt-Münster regimen (dexamethasone, vincristine, methotrexate, ifosfamide, cytarabine, L-asparaginase, cyclophosphamide, prednisone, daunorubicin, 6-thioguanine (6-TH), imatinib/dasatinib) for Ph-positive B-ALL; or
    • COG AALL0031 regimen + imatinib (ifosfamide, etoposide, methotrexate, hydrocortisone, cytarabine, imatinib or dasatinib, daunorubicin, cyclophosphamide, vincristine, L-asparaginase, dexamethasone) for Ph-positive B-ALL
    • COG AALL0622 regimen + dasatinib (high dose methotrexate, vincristine, daunorubicin, cyclophosphamide, pegaspargase/L-asparaginase, dexamethasone, cytarabine, dasatinib: IT therapy: ITT) for Ph-positive B-ALL; or
    • Total Therapy XVII regimen (SR/HR arm) + dasatinib (high-dose methotrexate, pegaspargase, 6-MP, dasatinib; ITT) for Ph-positive B-ALL; or
    • COG AALL1231 regimen (cyclophosphamide, cytarabine, 6-MP, pegaspargase, vincristine) for T-ALL; or
    • COG AALL0434 regimen (cyclophosphamide, cytarabine, 6-MP, pegaspargase, vincristine, nelarabine) for T-ALL; or
    • SJCRH regimen, based on Total Therapy XVII Protocol (high-dose methotrexate, 6-MP, pegaspargase) for T-ALL; or
    • Interfant regimens for infant ALL [intermediate risk and HR arms (cyclophosphamide, 6-MP, cytarabine, methotrexate, prednisone, pegaspargase), post-consolidation, and HR arm not undergoing HSCT (dexamethasone, 6-TG, vincristine, cytarabine, daunorubicin, pegaspargase, cytarabine, prednisone, cyclophosphamide, methotrexate, 6-MP)]; or
  • Therapy for relapsed/refractory Ph-negative B-ALL, or in combination with dasatinib or imatinib for relapsed/refractory Ph-positive B-ALL as a component of:
    • UKALL R3 backbone chemotherapy (Phase 1: dexamethasone, mitoxantrone, vincristine, pegasparaginase, IT methotrexate, Phase 2: dexamethasone, vincristine methotrexate, peg-asparaginase, cyclophosphamide, etoposide, IT methotrexate, Phase 3: dexamethasone vincristine, cytarabine,erwinase methotrexate IT methotrexate, Phase 4: fludarabine, cytarabine, liposomal daunorubicin, Phase 5: dexamethasone, 6-MP, vincristine, methotrexate, etoposide, cyclophosphamide, cytarabine, IT methotrexate, Phase 6: dexamethasone, vincristine, 6-MP, methotrexate, IT methotrexate); or
    • COG AALL01P2 regimen (Block 1: vincristine, prednisone, pegasparaginase, doxorubicin, imatinib, IT: cytarabine, methotrexate, or ITT; Block 2: cyclophosphamide, etoposide, methotrexate, imatinib, G-CSF, IT: methotrexate, or ITT, Block 3: cytarabine, pegasparaginase, cytarabine, pegasparaginase, imatinib, G-CSF); or
    • ALL-REZ BFM 90 regimen (Block 1: dexamethasone, mercaptopurine, vincristine, methotrexate, cytarabine, pegasparaginase, IT: prednisolone, cytarabine, methotrexate Block 2: dexamethasone, thioguanine, vindesine, methotrexate, daunorubicin, ifosfamide, pegasparaginase, IT: prednisolone, cytarabine, methotrexate, Block 3: dexamethasone, cytarabine, etoposide, pegasparaginase, IT: prednisolone, cytarabine, methotrexate); or
    • COG AALL07P1 regimen (Block 1 vincristine, doxorubicin, prednisone, bortezomib, pegaspargase, IT: cytarabine, methotrexate, or ITT Block 2 etoposide, cyclophosphamide, bortezomib, G-CSF, high-dose methotrexate, leucovorin IT: methotrexate or ITT Block 3 cytarabine, pegasparaginase, G-CSF); or
    • high-dose cytarabine-based regimens (eg, high-dose cytarabine, pegasparaginase); or
  • Therapy for relapsed/refractory T-ALL as a component of:
    • A bortezomib-containing regimen (e.g. bortezomib, vincristine, doxorubicin, pegaspargase, and prednisone or dexamethasone); or
    • UKALL R3 Block 1 (dexamethasone, mitoxantrone, pegaspargase, and vincristine); or
    • BFM Intensification Block 1 (high-dose methotrexate, high-dose cytarabine, dexamethasone, vincristine, pegaspargase, and cyclophosphamide); or

Acute Lymphoblastic Leukemia, ALL, Adult and Adolescent

  • Induction/consolidation therapy for Philadelphia chromosome-negative ALL as a component of:
    • CALGB 10403 regimen (daunorubicin, vincristine, prednisone, and pegaspargase) (patients aged less than 40 years); or
    • COG AALL0232 regimen (daunorubicin, vincristine, prednisone, and pegaspargase) (individuals aged less than or equal to 21 years); or
    • COG AALL0434 regimen (daunorubicin, vincristine, prednisone, and pegaspargase; nelarabine added to consolidation) (for T-ALL); or
    • DFCI ALL regimen based on DFCI Protocol 00-01 (doxorubicin, vincristine, prednisone, high-dose methotrexate, and pegaspargase) (individuals aged less than 50 years); or
    • GRAALL-2005 regimen (daunorubicin, vincristine, prednisone, pegaspargase, and cyclophosphamide) with rituximab for CD20-positive disease (individuals aged less than 60 years); or
    • PETHEMA ALL-96 regimen (daunorubicin, vincristine, prednisone, pegaspargase, and cyclophosphamide) (individuals aged less than 30 years); or
    • USC ALL based on CCG-1882 regimen (daunorubicin, vincristine, prednisone, and methotrexate with augmented pegaspargase) (individuals aged 18-57 years); or
    • Linker 4-drug regimen (daunorubicin, vincristine, prednisone, pegaspargase); or
  • Induction/consolidation therapy for Philadelphia chromosome-negative ALL in adult individuals as a component of:
    • CALGB 8811 Larson regimen (daunorubicin, vincristine, prednisone, pegaspargase, and cyclophosphamide); or
    • GRAALL-2005 regimen (daunorubicin, vincristine, prednisone, pegaspargase, and cyclophosphamide) with rituximab for CD20-positive disease (individuals aged  less than 60 years); or
    • Linker 4-drug regimen (daunorubicin, vincristine, prednisone, and pegaspargase) for individuals aged less than 60 years of age; or
    • MRC UKALLXII/ECOG2993 regimen (daunorubicin, vincristine, prednisone, and pegaspargase) (induction phase I); or
  • Induction therapy for Philadelphia chromosome-negative ALL in adults aged greater than or equal to 65 years as a component of CALGB 9111 regimen (cyclophosphamide, daunorubicin, vincristine, prednisone, and pegaspargase) (high intensity); or
  • 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); or
    • MOpAD regimen (methotrexate, vincristine, pegaspargase, dexamethasone) with rituximab for CD20-positive disease; or
  • Therapy for relapsed/refractory Philadelphia chromosome-positive ALL as a component of MOpAD regimen (methotrexate, vincristine, pegaspargase, dexamethasone) with rituximab for CD20-positive disease and TKI; or
  • Central nervous system directed therapy as systemic chemotherapy for ALL; or

Acute Myeloid Leukemia, AML

  • Treatment of individuals with blastic plasmacytoid dendritic cell neoplasm (BPDCN) for:
    • Treatment induction in individuals who are candidates for intensive remission therapy; or
    • Treatment for relapsed/refractory disease (if not already used) as a component of AspaMetDex (pegaspargase, methotrexate, dexamethasone); or

T-Cell Lymphomas, Extranodal NK/T-Cell Lymphoma, nasal type

  • For the treatment of non-hodgkin’s Lymphoma – Extranodal NK/T-Cell Lymphoma, nasal type:
    • Used as a component of SMILE (dexamethasone, methotrexate, ifosfamide, pegaspargase, and etoposide) regimen as:
      • Induction therapy followed by radiation for stage I-II nasal disease in individuals fit for chemotherapy; or
      • Induction therapy as a component of combination chemotherapy with or without radiation for stage IV nasal disease or stage I-IV extranasal disease; or
      • Additional therapy (if regimen not previously used) in individuals with a positive biopsy following partial response to induction therapy or no response to induction therapy; or
    • When used as a component of P-GEMOX (gemcitabine, pegaspargase, and oxaliplatin) regimen as:
      • Induction therapy as a component of sandwich chemoradition (preceding and following radiation) for stage I-II nasal disease in individuals who are fit for chemotherapy but are unable to tolerate intense chemotherapy; or
      • Additional therapy (if regimen not previously used) in individuals with a positive biopsy following partial response to induction therapy or no response to induction therapy; or
    • As a component of AspaMetDex (pegaspargase, methotrexate, and dexamethasone) regimen for:
      • Induction therapy as a component of combination chemotherapy with or without radiation for stage IV extranasal disease
      • Additional therapy (if regimen not previously used in individuals with a positive biopsy following partial response to induction therapy or no response to induction therapy.

Pegaspargase (Oncaspar) is considered experimental/investigational for any other indication and therefore non-covered.

Procedure Codes

J9266

Asparaginase Erwinia Chrysanthemi (Erwinaze) may be considered medically necessary for any of the following:

FDA Indications

  • In combination with other chemotherapeutic agents in individuals with ALL who have developed hypersensitivity to E. coli-derived asparaginase; or

 

NCCN Indications

  • As a substitute for pegaspargase in cases of systemic allergic reaction or anaphylaxis due to pegaspargase hypersensitivity in individuals with ALL; or
  • As a substitute for pegaspargase in cases of systemic allergic reaction or anaphylaxis due to pegaspargase hypersensitivitu in individuals with pediatric ALL; or
  • As induction therapy in adult individuals age greater than or equal to 65 years of age with ALL as a component of:
    • PETHEMA-based regimen such as ALLOLD07 (vincristine, dexamethasone, idarubicin, cyclophosphamide, cytarabine, methotrexate, and L-asparaginase) (moderate intensity) for Philadelphia chromosome-negative ALL; or
    • Modified DFCI 91-01 protocol: dexamethasone, doxorubicin, vincristine, methotrexate, cytarabine, L-asparaginase, and IT chemotherapy) (moderate intensity) for Philadelphia chromosome-negative ALL; or
    • EWALL: TKI (dasatinib, nilotinib) with multiagent chemotherapy (vincristine, dexamethasone, methotrexate, cytarabine, asparaginase) (moderate intensity) for Philadelphia chromosome-positive ALL.

Asparaginase Erwinia Chrysanthemi (Erwinaze) is considered experimental/investigational for any other indication and therefore non-covered.  Scientific evidence does not support its use for any other indications.

Procedure Codes

J9019

Calasparagase pegol-mknl (Asparlas) may be considered medically necessary for ANY of the following indications:

FDA Indications

  • As a component of a multi-agent chemotherapeutic regimen for the treatment of ALL in individuals age one (1) month to 21 years of age; or

 

NCCN Indications

  • As a substitute for pegaspargase (Oncaspar) in individuals age one (1) month to 21 years of age with pediatric ALL for more sustained asparaginase activitiy; or
  • As a substitute for pegaspargase (Oncaspar) in individuals less than or equal to 21 years of age with ALL for more sustained asparaginase activitiy.

Calasparagase pegol-mknl (Asparlas) is considered experimental/investigational for any other indication and therefore non-covered.  Scientific evidence does not support its use for any other indications.

Procedure Codes

J9118

NOTE: In addition to the above criteria, product specific dosage and/or frequency limits may apply in accordance with the U.S. Food and Drug Administration (FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services (CMS) and other peer reviewed resources or evidence-based guidelines. Blue Cross Blue Shield of North Dakota may deny, in full or in part, reimbursement for utilization that does not fall within the applicable dosage and/or frequency limits.

Diagnosis Codes

Covered Diagnosis Codes for procedure code J9266

C83.50 C83.51 C83.52 C83.53 C83.54 C83.55 C83.56
C83.57 C83.58 C83.59 C84.90 C84.91 C84.92 C84.93
C84.94 C84.95 C84.96 C84.97 C84.98 C84.99 C84.Z0
C84.Z1 C84.Z2 C84.Z3 C84.Z4 C84.Z5 C84.Z6 C84.Z7
C84.Z8 C84.Z9 C86.0 C86.4 C91.00 C91.01 C91.02

Covered Diagnosis Codes for procedure code J9019

C83.50 C83.51 C83.52 C83.53 C83.54 C83.55 C83.56
C83.57 C83.58 C83.59 C91.00 C91.01 C91.02

Covered Diagnosis Codes for procedure code J9118

C83.50 C83.51 C83.52 C83.53 C83.54 C83.55 C83.56
C83.57 C83.58 C83.59 C91.00 C91.01 C91.02

Professional Statements and Societal Positions Guidelines

NA

Links