See Important Reminder at the end of this policy for important regulatory and legal information.

Transcription

1 Clinical Policy: Immunoglobulin for Paraneoplastic Disorders Reference Number: CP.CPA.89 Effective Date: Last Review Date: Line of Business: Commercial Revision Log See Important Reminder at the end of this policy for important regulatory and legal information. Description The following are Immunoglobulin agents requiring prior authorization: Human Immunoglobulin G Injection (Bivigam ), Immune Globulin Intravenous (Carimune NF ), Immune Globulin Intravenous (Flebogamma ), Immune Globulin Infusion (Gammagard Liquid ), Immune Globulin Intravenous (Gammagard S/D ), Immune Globulin Injection (Gammaked ), Immune Globulin Intravenous (Gammaplex ), Immune Globulin Injection (Gamunex -C), Immune Globulin Intravenous (Octagam ), Immune Globulin Intravenous (Privigen ), Immune Globulin Subcutaneous (Hizentra, Cuvitru ), Immune Globulin Infusion with Recombinant Human Hyaluronidase (Hyqvia) FDA approved indication Immune globulin intravenous: Bivigam, Carimune NF, Flebogamma, Gammaplex, Octagam, Privigen (including Gamunex-C, Gammaked and Gammagard S/D when used intravenously) are indicated: Replacement therapy for primary immunodeficiency (PI) This includes, but is not limited to, congenital agammaglobulinemia, common variable immunodeficiency, X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies For the of patients with idiopathic thrombocytopenic purpura (also known as primary immune thrombocytopenia or chronic immune thrombocytopenic purpura) (ITP) to raise platelet counts to prevent bleeding or to allow a patient with ITP to undergo surgery. Maintenance therapy to improve muscle strength and disability in adult patients with Multifocal Motor Neuropathy (MMN) For prevention of bacterial infections in patients with hypogammaglobulinemia and/or recurrent bacterial infections associated with B-cell chronic lymphocytic leukemia (CLL) For prevention of coronary artery aneurysms associated with Kawasaki syndrome For of chronic inflammatory demyelinating polyneuropathy (CIDP) to improve neuromuscular disability and impairment and for maintenance therapy to prevent relapse. Immune globulin subcutaneous: Hizentra, Hyqvia, Cuvitru (including Gamunex-C, Gammaked, and Gammagard Liquid when used subcutaneously) are indicated: For the of/replacement therapy for patients with primary immunodeficiency (PI). This includes, but is not limited to, congenital agammaglobulinemia, common variable immunodeficiency (CVID), X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies Limitation of use: Hyqvia: safety and efficacy of chronic use of recombinant human hyaluronidase in Hyqvia have not been established in conditions other than PI. Page 1 of 11

2 Policy/Criteria Provider must submit documentation (which may include office chart notes and lab results) supporting that member has met all approval criteria. It is the policy of health plans affiliated with Centene Corporation Bivigam, Carimune NF, Flebogamma, Gammagard Liquid, Gammagard S/D, Gammaked, Gammaplex, Gamunex-C, Octagam, Privigen, Hizentra and Hyqvia are medically necessary when the following criteria are met: I. Initial Approval Criteria A. Paraneoplastic Neurological Syndrome Opsoclonus-Myoclonus-Syndrome (must meet all): 1. Diagnosis of paraneoplastic neurological syndrome opsoclonus-myoclonussyndrome; 2. Failure of maximally tolerated doses of adrenocorticotropic hormone (ACTH) and corticosteroids unless contraindicated or clinically significant adverse effects are experienced; 3. Dose does not exceed: a. IVIG: 2 g/kg per month b. IGSC (including Gamunex, Gammaked, Gammagard Liquid): 200 mg/kg per week c. Hizentra: [Previous IVIG dose x 1.37] # of weeks between doses based on IVIG d. Hyqvia: 600 mg/kg at 3 to 4 week intervals e. Cuvitru: [Previous IVIG dose x 1.30] # of weeks between doses based on IVIG Approval duration: 6 months or to member s renewal period, whichever is longer B. Paraneoplastic Neurological Syndrome Anti-NMDA Encephalitis (must meet all): 1. Diagnosis of paraneoplastic neurological syndrome anti-nmda encephalitis; 2. Dose does not exceed: a. IVIG: 0.4 g/kg per day b. IGSC (including Gamunex, Gammaked, Gammagard Liquid) : 200 mg/kg per week c. Hizentra: [Previous IVIG dose x 1.37] # of weeks based on previous IVIG interval d. Hyqvia: 600 mg/kg at 3 to 4 week intervals e. Cuvitru: [Previous IVIG dose x 1.30] # of weeks between doses based on IVIG Approval duration: 6 months or to member s renewal period, whichever is longer C. Other diagnoses/indications 1. Refer to CP.CPA.09 if diagnosis is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized). Page 2 of 11

3 II. Continued Therapy A. Paraneoplastic Neurological Syndrome Opsoclonus-Myoclonus-Syndrome (must meet all): 1. Currently receiving medication via health plan benefit or member has previously met initial approval criteria; 2. Documentation of positive response to therapy; 3. Dose does not exceed: a. IVIG: 2 g/kg over 6 hours per month b. IGSC (including Gamunex, Gammaked, Gammagard Liquid): 200 mg/kg per week c. Hizentra: [Previous IVIG dose x 1.37] # of weeks between doses based on IVIG d. Hyqvia: 600 mg/kg at 3 to 4 week intervals e. Cuvitru: [Previous IVIG dose x 1.30] # of weeks between doses based on IVIG Approval duration: 6 months or to member s renewal period, whichever is longer B. Paraneoplastic Neurological Syndrome Anti-NMDA Encephalitis (must meet all): 1. Currently receiving medication via health plan benefit or member has previously met initial approval criteria; 2. Documentation of positive response to therapy; 3. Dose does not exceed: a. IVIG: 0.4 g/kg per day b. IGSC (including Gamunex, Gammaked, Gammagard Liquid) c. Hizentra: [Previous IVIG dose x 1.37] # of weeks based on previous IVIG interval d. Hyqvia: 600 mg/kg at 3 to 4 week intervals e. Cuvitru: [Previous IVIG dose x 1.30] # of weeks between doses based on IVIG Approval duration: 6 months or to member s renewal period, whichever is longer C. Other diagnoses/indications (must meet 1 or 2): 1. Currently receiving medication via health plan benefit and documentation supports positive response to therapy. Approval duration: Duration of request or 12 months (whichever is less); or 2. Refer to CP.CPA.09 if diagnosis is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized). III. Diagnoses/Indications for which coverage is NOT authorized: A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policy CP.CPA.09 or evidence of coverage documents; B. A list of specific indications for which coverage is not authorized may be found in the PA guideline: CP.CPA.191 Immune Globulin Conditions Not Medically Necessary; C. Paraneoplastic cerebellar degeneration; D. Opsoclonus-myoclonus syndrome (OMS) with anti-yo Ab (also known as APCA); Page 3 of 11

4 E. Paraneoplastic encephalomyelitis/sensory neuropathy (PEM/SN) with anti-hu Ab (also known as ANNA-1); F. Paraneoplastic encephalomyelitis; G. Paraneoplastic sensory neuropathy or polyneuropathy; IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key PI: primary humoral immunodeficiency CVID: common variable immunodeficiency ITP: thrombocytopenic purpura MMN: multifocal motor neuropathy CLL: chronic lymphocytic leukemia (CLL) CIDP: chronic inflammatory demyelinating polyneuropathy IVIG: intravenous immunoglobulin ACTH: adrenocorticotropic hormone NMDA: N-methyl-D-aspartate PEM/SN: paraneoplastic encephalomyelitis/sensory neuropathy OMS: opsoclonus-myoclonus-syndrome IGSC: immune globulin subcutaneous Appendix B: General Information Paraneoplastic syndromes are the remote effects of a cancer unrelated to the effects of the tumor or its metastasis. Sometimes they are associated with low immune globulin values and sometimes they are associated with autoantibodies. The combination of IVIG, cyclophosphamide, and methylprednisolone in patients with paraneoplastic cerebellar degeneration and antineuronal antibodies in is not effective. Anti-NMDA encephalitis i. Although no standard of care for anti-nmda encephalitis exists, on the basis of data from the reviews completed, concurrent IVIG (0.4 g/kg per day for 5 days) and methylprednisolone (1 g/day for 5 days) is preferred over plasma exchange. ii. If no response is seen after 10 days, a second-line therapy is started. iii. Although there is a paucity of randomized controlled and comparative trials regarding the use of IVIG for this disorder, because of the severity of anti- NMDA encephalitis and on the basis of data from the completed reviews and case series, it has been noted that individuals who received early tumor (usually with immunotherapy) had better outcome and fewer neurological relapses than the rest of the patients, iv. IVIG given concurrently with corticosteroids has been determined to assist with full or substantial recovery in approximately 75% of the individuals with anti- NMDA encephalitis. Opsoclonus-myoclonus-syndrome or "dancing eyes-dancing feet" syndrome is a rare neurological disorder that affects infants and young children and has been described in adult patients with cancer Page 4 of 11

5 i. The current therapeutic strategies for OMS provide a broad spectrum of nonselective immunotherapies, including noncytotoxic and cytotoxic drugs, intravenous immunoglobulins, ACTH and plasma exchange ii. Intravenous immunoglobulin G is occasionally used as an alternative to ACTH. iii. Altogether, the available evidence suggests that IVIG may be an effective in parainfectious and idiopathic OMS. iv. Treatment with IVIG has been reported in a few idiopathic adult-onset OMS cases in literature and they have concluded that idiopathic OMS presents an age dependent prognosis and immunotherapy. IVIG seems to be associated with a faster recovery. v. Trends in the standard of care of OMS report that ACTH, prednisone, and intravenous immunoglobulin were used with equal frequency, but ACTH was associated with the best early response Appendix C: Therapeutic Alternatives Drug Dosing Regimen Dose Limit/Maximum Dose systemic glucocorticoid (Various - prednisone, prednisolone, or methylprednisolone) An equivalent of prednisone 2 mg/kg per day with a prolonged taper over several months and pulsed dexamethasone therapy of 20 mg/m 2 for three days, N/A H.P. Acthar Gel (repository corticotropin) * given monthly Begin with 75 U/m 2 IM/SC BID for one week and subsequent tapers based upon clinical response for a total therapy period of 40 weeks, V. Dosage and Administration Bivigam, Carimune NF, Flebogamma, Gammagard S/D, Gammaplex, Octagam, Privigen Anti-NMDA Encephalitis Anti-NMDA Encephalitis 0.4 g/kg per day 0.4 g/kg IV per day for 5 days (with methylprednisolone 1 g/day for 5 days) N/A Opsoclonus-Myoclonus- Syndrome (IVIG) OMS 1-2 g/kg IV over 6 hours every month 2 g/kg over 6 hours per month Gammagard Liquid, Gammaked, Gamunex-C Anti-NMDA Encephalitis; IVIG Anti-NMDA Encephalitis 0.4 g/kg per day Page 5 of 11

6 Gammagard Liquid, Gammaked, Gamunex-C Opsoclonus-Myoclonus- Syndrome 0.4 g/kg per day for 5 days (with methylprednisolone 1 g/day for 5 days) OMS 1-2 g/kg IV over 6 hours every month 2 g/kg over 6 hours per month IGSC OMS 100 to 200 mg/kg body weight SC per week OR Initial weekly SC dose can be calculated by multiplying the previous IVIG dose by 1.37, and then dividing this dose into weekly doses based on the patient's previous IVIG interval. 200 mg/kg per week OR [Previous IVIG dose x 1.37] # of weeks based on previous IVIG interval Hizentra Anti-NMDA Encephalitis; Opsoclonus-Myoclonus- Syndrome (IGSC) Administer SC at regular intervals from daily up to every two weeks (biweekly). To calculate the initial weekly dose of Hizentra, multiply the previous IVIG dose in grams by the dose adjustment factor of 1.37; then divide this by the number of weeks between doses during the patient`s IVIG (i.e., 3 or 4). [Previous IVIG dose x 1.37] # of weeks between doses based on IVIG Weekly Dosing: Administer calculated weekly dose starting 1 week after the last IVIG infusion Biweekly Dosing: Administer twice the calculated weekly dose starting 1 or 2 weeks after the last IVIG infusion or 1 week after the last IGSC infusion. Frequent Dosing (2 to 7 times per week): Divide the calculated weekly dose by the desired number of times Page 6 of 11

7 Hizentra per week. Start Hizentra 1 week after the last IVIG or IGSC infusion. To convert the Hizentra dose (in grams) to milliliters (ml), multiply the calculated dose (in grams) by 5. Hyqvia Anti-NMDA Encephalitis; Opsoclonus-Myoclonus- Syndrome (IGSC) Infuse SC the two components of Hyqvia sequentially, beginning with the recombinant human hyaluronidase. Initiate the IGSC within 10 minutes of the recombinant human hyaluronidase infusion. 600 mg/kg at 3 to 4 week intervals after initial ramp up Initiation of Increase dose and frequency from a 1-week dose to a 3- or 4-week dose (see ramp-up schedule below) For patients previously on another IG, administer the first dose of Hyqvia approximately one week after the last infusion of their previous Initial dosage ramp-up schedule (e.g., every 4-week dosing): Week 1: [1-week dose interval] ¼ of target dose Week 2: [2-week dose interval] ½ of target dose Week 3: no infusion Week 4: [3-week dose interval] ¾ of target dose Week 5: no infusion Week 6: no infusion Week 7: [4-week dose interval] target dose, repeat every 4 weeks Switching from IGIV Administer at the same dose and frequency as the previous intravenous Page 7 of 11

8 Hyqvia, after the initial dose rampup Naïve to IG or switching from IGSC 300 to 600 mg/kg at 3 to 4 week intervals, after initial ramp-up Dose adjustments See details in prescribing information VI. Product Availability Drug Availability Bivigam Vial, liquid solution, 10% (1 g/10 ml)): 50 ml, 100 ml Carimune NF Vial, lyophilized powder: 3 g, 6 g, 12 g Cuvitru Vial, 20% (200 mg/ml) in 5 ml, 10 ml, 20 ml, 40 ml Flebogamma 5% Vial, liquid preparation, 5% (50 mg/ml): 10mL, 50mL, 100mL, 200mL, 400mL Flebogamma 10% Vial, liquid preparation, 10% (100 mg/ml): 50 ml, 100 ml, 200 ml Gammagard Liquid, Vial, liquid solution, 10% (1 g/10 ml): 10 ml, 25 ml, 50 ml, 100 ml, 200 ml, 300 ml Gammagard S/D, Bottle, solution, 5 g, 10 g Gammaked Vial, liquid solution, 10% (1 g/10 ml): 10 ml, 25 ml, 50mL, 100mL, 200mL Gammaplex Vial, liquid, 5% (50 mg/ml): 50 ml, 100 ml, 200 ml, 400 ml Gamunex -C, Vial, solution, 10% (1 g/10 ml): 10 ml, 25 ml, 50 ml, 100 ml, 200 ml, 400 ml Octagam 5% Bottle, liquid preparation, 5% (50 mg/ml): 20 ml, 50 ml, 100 ml, 200 ml, 500 ml Octagam 10% Bottle, liquid preparation, 5% (100 mg/ml): 20 ml, 50 ml, 100 ml, 200 ml Privigen Vial, liquid solution, 10% (100 mg/ml): 50 ml, 100 ml, 200 ml, 400 ml Hizentra Vial, liquid solution, 20% (0.2 g/ml): 5 ml, 10 ml, 20 ml, 50 ml Hyqvia Dual vial unit, solution: -10% IgG (1 g/10 ml): 25 ml, 50 ml, 100 ml, 200 ml, 300 ml -160 U/mL recombinant human hyaluronidase: 1.25 ml, 2.5 ml, 5 ml, 15 ml Page 8 of 11

9 VII. References 1. Micromedex Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed January 13, Immune Globulin. American Hospital Formulary Service Drug Information. Available at: Accessed January 13, Gammagard S/D [Prescribing Information] Westlake Village, CA: Baxalta US Inc.; October Gammaplex [Prescribing Information] Hertfordshire, United Kingdom: Bio Products Laboratory Limited; July Gamunex-C [Prescribing Information] Research Triangle Park, NC: Grifols Therapeutics Inc.; September Hizentra [Prescribing Information] Bern, Switzerland: CSL Behring AG; October Carimune NF [Prescribing Information] Bern, Switzerland: CSL Behring AG; November Privigen [Prescribing Information] Bern, Switzerland: CSL Behring AG; October Gammagard Liquid [Prescribing Information] Westlake Village, CA: Baxalta US Inc.; October Hayes. Medical Technology Directory. Intravenous Immunoglobulin for Neurological Diseases. February 6, Updated July 30, Blaes F. Paraneoplastic Neurological Syndromes - Diagnosis and Management. Alternatively "Diagnosis and Management of Paraneoplastic Neurological Syndrome." B Curr Pharm Des May 16. [Epub ahead of print] 12. Briani C, Vitaliani R, Grisold W, et al. Spectrum of paraneoplastic disease associated with lymphoma. Neurology. 2011;76(8): Clinical Pharmacology Web Site. Available at: Accessed January 13, Bivigam [Prescribing Information] Boca Raton, FL: Biotest Pharmaceuticals Corporation; April Flebogamma 5% DIF [Prescribing Information] Barcelona, Spain: Institutio Grifols, S.A.; April Flebogamma 10% DIF [Prescribing Information] Barcelona, Spain: Institutio Grifols, S.A.; January Gammaked [Prescribing Information] Research Triangle Park, NC: Grifolis Therapeutics Inc.; September Hyqvia [Prescribing Information] Westlake Village, CA: Baxalta US Inc.; April Octagam 5% [Prescribing Information] Hoboken, NJ: Octapharma USA Inc.; October Octagam 10% [Prescribing Information] Hoboken, NJ: Octapharma USA Inc.; November Privigen [Prescribing Information] Bern, Switzerland: CSL Behring AG; October Page 9 of 11

10 22. Cuvitru [Prescribing Information]. Westlake Village, CA: Baxalta US Inc.; September Reviews, Revisions, and Approvals Date P&T Approval Date Converted to new template; minor changes to verbiage and grammar. References updated Important Reminder This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health professional organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information. The Health Plan makes no representations and accepts no liability with respect to the content of any external information used or relied upon in developing this clinical policy. This clinical policy is consistent with standards of medical practice current at the time that this clinical policy was approved. Health Plan means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan s affiliates, as applicable. The purpose of this clinical policy is to provide a guide to medical necessity, which is a component of the guidelines used to assist in making coverage decisions and administering benefits. It does not constitute a contract or guarantee regarding payment or results. Coverage decisions and the administration of benefits are subject to all terms, conditions, exclusions and limitations of the coverage documents (e.g., evidence of coverage, certificate of coverage, policy, contract of insurance, etc.), as well as to state and federal requirements and applicable Health Plan-level administrative policies and procedures. This clinical policy is effective as of the date determined by the Health Plan. The date of posting may not be the effective date of this clinical policy. This clinical policy may be subject to applicable legal and regulatory requirements relating to provider notification. If there is a discrepancy between the effective date of this clinical policy and any applicable legal or regulatory requirement, the requirements of law and regulation shall govern. The Health Plan retains the right to change, amend or withdraw this clinical policy, and additional clinical policies may be developed and adopted as needed, at any time. This clinical policy does not constitute medical advice, medical or medical care. It is not intended to dictate to providers how to practice medicine. Providers are expected to exercise professional medical judgment in providing the most appropriate care, and are solely responsible for the medical advice and of members. This clinical policy is not intended to recommend for members. Members should consult with their treating physician in connection with diagnosis and decisions. Page 10 of 11

11 Providers referred to in this clinical policy are independent contractors who exercise independent judgment and over whom the Health Plan has no control or right of control. Providers are not agents or employees of the Health Plan. This clinical policy is the property of the Health Plan. Unauthorized copying, use, and distribution of this clinical policy or any information contained herein are strictly prohibited. Providers, members and their representatives are bound to the terms and conditions expressed herein through the terms of their contracts. Where no such contract exists, providers, members and their representatives agree to be bound by such terms and conditions by providing services to members and/or submitting claims for payment for such services Centene Corporation. All rights reserved. All materials are exclusively owned by Centene Corporation and are protected by United States copyright law and international copyright law. No part of this publication may be reproduced, copied, modified, distributed, displayed, stored in a retrieval system, transmitted in any form or by any means, or otherwise published without the prior written permission of Centene Corporation. You may not alter or remove any trademark, copyright or other notice contained herein. Centene and Centene Corporation are registered trademarks exclusively owned by Centene Corporation. Page 11 of 11