Prior Authorization Review Panel MCO Policy Submission

Transcription

1 Prior Authorization Review Panel MCO Policy Submission A separate copy of this form must accompany each policy submitted for review. Policies submitted without this form will not be considered for review. Plan: Aetna Better Health Submission Date: 01/02/2019 Policy Number: 0864 Policy Name: Erwinaze (asparaginase Erwinia chrysanthemi) Effective Date: Revision Date: 12/06/2018 Type of Submission Check all that apply: New Policy Revised Policy* Annual Review No Revisions *All revisions to the policy must be highlighted using track changes throughout the document. Please provide any clarifying information for the policy below: CPB 0864 Erwinaze (asparaginase Erwinia chrysanthemi) Revision History since last PARP submission: 09/27/ This CPB has been revised to state that Erwinaze is considered experimental and investigational for the treatment of brain tumors (e.g., medulloblastomas). 09/26/2019 Next tentative scheduled review date by Corporate. Name of Authorized Individual (Please type or print): Signature of Authorized Individual: Dr. Bernard Lewin, M.D. Revised 12/06/2018

2 Erwinaze (asparaginase Erwinia chrysanthemi) - Medical Clinical Policy Bulletins Aetna Page 1 of /06/ > ( Erwinaze (asparaginase Erwinia chrysanthemi) Clinical Policy Bulletins Medical Clinical Policy Bulletins Number: 0864 *Please see amendment for Pennsylvania Medicaid at the end of this CPB. Policy Aetna considers Erwinaze (asparaginase Erwinia chrysanthemi) medically necessary for persons with the following malignancies who are hypersensitive to Elspar (asparaginase Escherichia coli) or Oncaspar (pegaspargase) Acute lymphoblastic leukemia (ALL) Lymphoblastic lymphoma Extranodal NK/T-cell lymphoma, nasal type. and the following criteria are met: Policy History Last Review 09/27/2018 Effective: 09/30/201 Next Review: 09/26/2019 Review History The member has documented, Grade 2 to 4 hypersensitivity (based on Common Terminology Toxicity Criteria) as a result of prior treatment with Elspar (asparaginase Escherichia coli) or Oncaspar (pegaspargase); and The member is using Erwinaze (asparaginase Erwinia chrysanthemi) as a component of a multi agent chemotherapeutic regimen. Aetna considers continued use beyond 3 months medically necessary for persons with no evidence of disease progression relative to pre-treatment state. Definitions Additional Information

3 Erwinaze (asparaginase Erwinia chrysanthemi) - Medical Clinical Policy Bulletins Aetna Page 2 of /06/2019 Aetna considers Erwinaze (asparaginase Erwinia chrysanthemi) therapy not medically necessary for members who have experienced disease progression while on asparaginase-based therapy. Aetna considers Erwinaze experimental and investigational for persons with any of the following contraindications: Persons with a history of serious pancreatitis with prior asparaginasebased therapy Persons with a history of thrombosis with prior asparaginase-based therapy Persons with serious hemorrhagic events with prior asparaginase-based therapy Persons who are hypersensitive to Erwinaze. Aetna considers Erwinaze experimental and investigational for the treatment of all other indications (e.g., acute myeloid leukemia, brain tumors (e.g., medulloblastomas)) because its effectiveness for these indications has not been established. Background Erwinaze (asparaginase Erwinia chrysanthemi) catalyzes the deamidation of asparagineto aspartic acid and ammonia, resulting in a reduction in circulating levels of asparagine. The mechanism of action of Erwinaze (asparaginase Erwinia chrysanthemi)is thought to be based on the inability of leukemic cells to synthesize asparagine due to lack of asparagine synthetase activity, resulting in cytotoxicity specific for leukemic cells that depend on an exogenous source of the amino acid asparagine for their protein metabolism and survival. Erwinaze (asparaginase Erwinia chrysanthemi) is an asparagine specific enzyme that has been approved by the U.S. Food and Drug Administration (FDA) a component of a multi agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to E. coliderived asparaginase. The National Comprehensive Cancer Network Drugs and Biologics Compendium (NCCN, 2018) recommends that Erwinaze can be substituted for pegaspargase in cases of systemic allergic reaction or anaphylaxis due to pegaspargase hypersensitivity. The NCCN Drug and Biologics Compendium (NCCN,

4 Erwinaze (asparaginase Erwinia chrysanthemi) - Medical Clinical Policy Bulletins Aetna Page 3 of /06/ ) recommends pegasparaginase (Oncospar) for acute lymphoblastic leukemia and for extranodal NK/T-Cell Lymphoma, nasal type The NCCN Drugs and Biologics Compendium (NCCN, 2016) recommends asparaginase (Elspar) for lymphoblastic lymphoma. Serious hypersensitivity reactions, including anaphylaxis have occurred after the use of Erwinaze (asparaginase Erwinia chrysanthemi) in 5% of patients in clinical trials.administer this product in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis. If a serious hypersensitivity reaction occurs, discontinue Erwinaze (asparaginase Erwinia chrysanthemi) and initiate appropriate therapy. Pancreatitis has been reported with Erwinaze (asparaginase Erwinia chrysanthemi) therapy in 4% of patients in clinical trials. Evaluate patients with symptoms compatible with pancreatitis to establish a diagnosis. Discontinue Erwinaze (asparaginase Erwiniachrysanthemi) for severe or hemorrhagic pancreatitis manifested by abdominal pain >72 hours and amylase elevation 2.0 x ULN. Severe pancreatitis is a contraindication to additional asparaginase administration. In the case of mild pancreatitis, hold Erwinaze (asparaginase Erwinia chrysanthemi) until the signs and symptoms subside and amylase levels return to normal. After resolution, treatment with Erwinaze (asparaginase Erwinia chrysanthemi) may be resumed. Glucose intolerance has been reported with Erwinaze (asparaginase Erwinia chrysanthemi) therapy in 2% of patients in clinical trials, and, in some cases, may beirreversible. Monitor glucose levels in patients at baseline and periodically during treatment. Administer insulin therapy as necessary in patients with hyperglycemia. Serious thrombotic events, including sagittal sinus thrombosis have been reported with both E. coli and Erwinia derived L asparaginase therapy. The following coagulation proteins were decreased in the majority of patients after a 2 week course of Erwinaze (asparaginase Erwinia chrysanthemi): fibrinogen, protein C activity, protein S activity,and anti thrombin III. Discontinue Erwinaze (asparaginase Erwinia chrysanthemi) for athrombotic or hemorrhagic event until symptoms resolve; after resolution, treatment with Erwinaze (asparaginase Erwinia chrysanthemi) may be resumed. Acute Myeloid Leukemia:

5 Erwinaze (asparaginase Erwinia chrysanthemi) - Medical Clinical Policy Bulletins Aetna Page 4 of /06/2019 Emadi et al (2014) stated that asparaginases are among the most effective agents against acute lymphoblastic leukemia (ALL) and are Food and Drug Administration (FDA)-approved for the treatment of pediatric and adult ALL. However, the effectiveness of these drugs for the treatment of other hematologic malignancies particularly acute myeloid leukemia (AML) is not well-established. The mechanism of action of asparaginases has thought to be related to a swift and sustained reduction in serum L-asparagine, which is required for rapid proliferation of metabolically demanding leukemic cells. However, asparagine depletion alone appears not to be sufficient for effective cytotoxic activity of asparaginase against leukemia cells, because glutamine can rescue asparagine-deprived cells by regeneration of asparagine via a transamidation chemical reaction. For this reason, glutamine reduction is also necessary for full anti-leukemic activity of asparaginase. Indeed, both Escherichia coli and Erwinia chrysanthemi asparaginases possess glutaminase enzymatic activity, and their administrations have shown to reduce serum glutamine level by deamidating glutamine to glutamate and ammonia. Emerging data have provided evidence that several types of neoplastic cells require glutamine for the synthesis of proteins, nucleic acids, and lipids. This fundamental role of glutamine and its metabolic pathways for growth and proliferation of individual malignant cells may identify a special group of patients whose solid or hematologic neoplasms may benefit significantly from interruption of glutamine metabolism. The authors stated that asparaginase products deserve a second look particularly in non-all malignant blood disorders. Emadi and associates (2018) stated that depletion of glutamine (Gln) has emerged as a potential therapeutic approach in the treatment of AML, as neoplastic cells require Gln for synthesis of cellular components essential for survival. Asparaginases deplete Gln, and asparaginase derived from Erwinia chrysanthemi (Erwinaze) appears to have the greatest glutaminase activity of the available asparaginases. In this phase-i study, these researchers determined the dose of Erwinaze that safely and effectively depletes plasma Gln levels to less than or equal to 120 μmol/l in patients with relapsed or refractory (R/R) AML. A total of 5 patients were enrolled before the study was halted due to issues with Erwinaze manufacturing supply. All patients received Erwinaze at a dose of 25,000 IU/m2 intravenously 3 times weekly for 2 weeks. Median trough plasma Gln level at 48 hours after initial Erwinaze administration was 27.6 μmol/l, and 80 % (lower limit of 1-sided 95 % confidence interval [CI]: 34 %) of patients achieved at least 1 undetectable plasma Gln value (less than 12.5 μmol/l), with the fold reduction (FR) in Gln level at 3 days, relative to baseline, being 0.16 (p < for rejecting FR =

6 Erwinaze (asparaginase Erwinia chrysanthemi) - Medical Clinical Policy Bulletins Aetna Page 5 of /06/2019 1). No dose-limiting toxicities (DLTs) were identified; 2 patients responded, 1 achieved partial remission (PR) and 1 achieved hematologic improvement after 6 doses of Erwinaze monotherapy. The authors concluded that these findings suggested that asparaginase-induced Gln depletion may have an important role in the management of patients with AML, and supported more pharmacologic and clinical studies on the mechanistically designed asparaginase combinations in AML. Brain Tumors (e.g., Medulloblastomas): Sanghez and colleagues (2018) noted that anti-metabolites are less myelosuppressive than DNA-damaging anti-cancer drugs and may be useful against brain tumors. These researchers evaluated the asparagine/glutaminedeaminating agent Erwinaze with/without temozolomide against brain tumor cells and mouse medulloblastomas. Erwinaze treatment of cell lines and neuro-spheres led to dose-dependent reductions of cells (reversible by L-glutamine), with half maximal inhibitory concentrations (IC50s) of 0.12 to greater than 10 IU/ml. Erwinaze at less than 1 IU/ml reduced temozolomide IC50s by 3.6- to 13-fold (300 to 1,200 μm to 40 to 330 μm). In this study, 7-week-old SMO/SMO mice treated with Erwinaze (regardless of temozolomide treatment) had better survival 11 weeks post-therapy, compared to those not treated with Erwinaze (81.25 % versus %, p = 0.08). Temozolomide-treated mice developed 10 % weight loss, impairing survival. All 16 mice treated with temozolomide (regardless of Erwinaze treatment) succumbed by 40 weeks of age, whereas 5/8 animals treated with Erwinaze alone and 2/6 controls survived (p = 0.035). The authors concluded that erwinaze enhanced cytotoxicity of temozolomide in-vitro, and improved survival in SMO/SMO mice, likely by reducing cerebrospinal fluid (CSF) glutamine. Moreover, temozolomide-associated toxicity prevented demonstration of any potential combinatorial advantage with Erwinaze in-vivo. Appendix The FDA-approved labeling of Erwinaze recommends the following dosages: To substitute for a dose of pegaspargase:the recommended dose is 25,000 International Units/m2 administered intramuscularly three times a week (Monday/Wednesday/Friday) for six doses for each planned dose of pegaspargase.

7 Erwinaze (asparaginase Erwinia chrysanthemi) - Medical Clinical Policy Bulletins Aetna Page 6 of /06/2019 To substitute for a dose of native E. coli asparaginase: The recommended dose is 25,000 International Units/m2 administered intramuscularly for each scheduled dose of native E. coli asparaginase. Table: Common Terminology Criteria for Adverse Events v4.03 (CTCAE) Grade Signs and Transient Intervention or Prolonged (e.g., not Life-threatening Death symptoms flushing or infusion rapidly responsive consequences; rash; drug interruption to symptomatic urgent fever <38 C indicated; medication and/or intervention (<100.4 F) responds brief interruption of indicated intervention promptly to infusion; recurrence not indicated symptomatic of symptoms treatment; following initial prophylactic improvement; medications hospitalization indicated for < indicated for clinical 24 hours sequelae CPT Codes / HCPCS Codes / ICD-10 Codes Information in the [brackets] below has been added for clarification purposes. Codes requiring a 7th character are represented by "+": Code Code Description Other CPT codes related to the CPB: Chemotherapy administration, subcutaneous or intramuscular; nonhormonal anti-neoplastic Chemotherapy administration; intravenous, push technique, single or initial substance/drug intravenous, push technique, each additional substance/drug (List separately in addition to code for primary procedure) Chemotherapy administration; intravenous infusion technique HCPCS codes covered if selection criteria are met: J9019 Injection, asparaginase, (Erwinaze), 1,000 iu Other HCPCS codes related to the CPB:

8 Erwinaze (asparaginase Erwinia chrysanthemi) - Medical Clinical Policy Bulletins Aetna Page 7 of /06/2019 Code Code Description J9020 Injection, asparaginase, not otherwise specified, 10,000 units [Elspar] J9266 Injection, pegaspargase, per single dose vial [Oncaspar] ICD-10 codes covered if selection criteria are met: C C83.59 Lymphoblastic (diffuse) lymphoma C86.0 Extranodal NK/T-Cell Lymphoma, nasal type C C91.02 Acute lymphoblastic leukemia [ALL] ICD-10 codes not covered for indications listed in the CPB: C C83.39, C C85.99, C86.1 Lymphosarcoma and reticulosarcoma and other specified malignant tumors of lymphatic tissue [excluding ALL, lymphoblastic lymphoma, extranodal NK/T-Cell Lymphoma, nasal type] - C90.32, C C91.92 ICD-10 codes contraindicated for this CPB: I I66.9 Occlusion and stenosis of cerebral artery I I74.4 Embolism and thrombosis of arteries of the extremities I81 Portal vein thrombosis I I82.91 Other venous embolism and thrombosis K K85.92 Pancreatitis T Adverse effect of other drugs, medicaments and biological substances [hypersensitivity to Erwinase] The above policy is based on the following references: 1. EUSA Pharma (USA), Inc. Erwinaze (asparaginase Erwinia chrysanthemi) for injection, intramuscular use. Prescribing Information. Langhorne, PA: EUSA Pharma; revised November National Comprehensive Cancer Network (NCCN). Acute lymphoblastic leukemia. NCCN Clinical Practice Guidelines in Oncology, v Fort Washington, PA: NCCN; Moscardo Guilleme C, Fernandez Delgado R, Sevilla Navarro J, et al. Update on L-asparaginase treatment in paediatrics. An Pediatr (Barc). 2013;79(5):329.e1-329.e11.

9 Erwinaze (asparaginase Erwinia chrysanthemi) - Medical Clinical Policy Bulletins Aetna Page 8 of /06/ Salzer WL, Asselin B, Supko JG, et al. Erwinia asparaginase achieves therapeutic activity after pegaspargase allergy: A report from the Children's Oncology Group. Blood. 2013;122(4): Keating GM. Asparaginase Erwinia chrysanthemi (Erwinaze ): A guide to its use in acute lymphoblastic leukemia in the USA. BioDrugs. 2013;27(4): Emadi A, Zokaee H, Sausville EA. Asparaginase in the treatment of non-all hematologic malignancies. Cancer Chemother Pharmacol. 2014;73(5): National Comprehensive Cancer Network (NCCN). Asparaginase. NCCN Drugs and Biologics Compendium. Fort Washington, PA: NCCN; National Comprehensive Cancer Network (NCCN). Pegaspargase. NCCN Drugs and Biologics Compendium. Fort Washington, PA: NCCN; National Comprehensive Cancer Network (NCCN). Asparaginase Erwinia chrysanthemi. NCCN Drugs and Biologics Compendium. Fort Washington, PA: NCCN; Vrooman LM, Kirov II, Dreyer ZE, et al. Activity and toxicity of intravenous Erwinia asparaginase following allergy to E. coli-derived asparaginase in children and adolescents with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2016;63(2): Figueiredo L, Cole PD, Drachtman RA. Asparaginase Erwinia chrysanthemi as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia who have developed hypersensitivity to E. coli-derived asparaginase. Expert Rev Hematol. 2016;9(3): Emadi A, Law JY, Strovel ET, et al. Asparaginase erwinia chrysanthemi effectively depletes plasma glutamine in adult patients with relapsed/refractory acute myeloid leukemia. Cancer Chemother Pharmacol. 2018;81(1): Sanghez V, Chen M, Li S, et al. Efficacy of asparaginase erwinia chrysanthemi with and without temozolomide against glioma cells and intracranial mouse medulloblastoma. Anticancer Res. 2018;38(5):

10 Erwinaze (asparaginase Erwinia chrysanthemi) - Medical Clinical Policy Bulletins Aetna Page 9 of /06/2019 Copyright Aetna Inc. All rights reserved. Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change. Copyright Aetna Inc.

11 AETNA BETTER HEALTH OF PENNSYLVANIA Amendment to Aetna Clinical Policy Bulletin Number: 0864 Erwinaze (asparaginase Erwinia chrysanthemi) There are no amendments for Medicaid. Revised 12/06/2018