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Date Printed: August 18, 2017: 07:55 PM

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This medical policy (medical coverage guideline) is Copyright 2017, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

09-J0000-63

Original Effective Date: 11/15/00

Reviewed: 04/10/13

Revised: 11/01/15

Subject: Oprelvekin; Interleukin 11 (Neumega®)

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Position Statement Dosage/ Administration Billing/Coding Reimbursement Program Exceptions Definitions
           
Related Guidelines Other References Updates
           

DESCRIPTION:

Neumega® is a thrombopoietic growth factor that directly stimulates the production, differentiation, and maturation of megakaryocytes and platelets. Neumega® is indicated for the prevention of severe thrombocytopenia and the reduction of the need for platelet transfusions following myelosuppressive chemotherapy in members with nonmyeloid malignancies who are at high risk of severe thrombocytopenia.

Oprelvekin, the active ingredient in Neumega®, is produced in Escherichia coli (E. coli) by recombinant DNA technology. The protein has a molecular mass of approximately 19,000 daltons, and is non-glycosylated. The polypeptide is 177 amino acids in length and differs from the 178 amino acid length of native IL-11 only in lacking the amino-terminal praline residue. This alteration has not resulted in measurable differences in bioactivity either in vitro or in vivo.

The primary hematopoietic activity of oprelvekin is stimulation of megakaryocytopoiesis and thrombopoiesis. Neumega has shown potent thrombopoietic activity in animal models of compromised hematopoiesis, including moderately to severely myelosuppressed mice and nonhuman primates. In these models, oprelvekin improved platelet nadirs and accelerated platelet recoveries compared to controls.

POSITION STATEMENT:

Neumega® (oprelvekin) meets the definition of medical necessity when the following criteria are met:

Oprelvekin is considered experimental or investigational when administered for all other conditions, as there is insufficient clinical evidence to support its use.

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE.

The recommended dose of oprelvekin in adults without severe renal impairment is 50 mcg/kg given once daily. Oprelvekin should be administered subcutaneously as a single injection in either the abdomen, thigh, or hip (or upper arm if not self-injecting). A safe and effective dose has not been established in children.

The recommended dose of oprelvekin in adults with severe renal impairment (creatinine clearance <30 mL/min) is 25 mcg/kg. An estimate of the member's creatinine clearance (CLcr) in mL/min is required. CLcr in mL/min may be estimated from a spot serum creatinine (mg/dL) determination using the following formula:

 

[140 - age (years)] x weight (kg)

 

CLcr =

−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−

{x 0.85 for female members}

 

72 x serum creatinine (mg/dL)

 

Dosing should be initiated six to 24 hours after the completion of chemotherapy. Platelet counts should be monitored periodically to assess the optimal duration of therapy. Dosing should be continued until the post-nadir platelet count is ≥50,000/μL. In controlled clinical trials, doses were administered in courses of 10 to 21 days. Dosing beyond 21 days per treatment course is not recommended.

Treatment with oprelvekin should be discontinued at least two days before starting the next planned cycle of chemotherapy.

PRECAUTIONS:

WARNING

Allergic Reactions Including Anaphylaxis

Oprelvekin has caused allergic or hypersensitivity reactions, including anaphylaxis. Administration of oprelvekin should be permanently discontinued in any member who develops an allergic or hypersensitivity reaction.

Cardiovascular effects: Oprelvekin use is associated with cardiovascular reactions, including arrhythmias and pulmonary edema. Cardiac arrest has been reported, but the causal relationship to oprelvekin is uncertain. Use with caution in members with a history of atrial arrhythmias, and only after consideration of the potential risks in relation to anticipated benefit. In clinical trials, cardiac reactions, including atrial arrhythmias (atrial fibrillation or atrial flutter), occurred in 23 of 157 (15%) members treated with oprelvekin at doses of 50 mcg/kg. Arrhythmias were usually brief in duration; conversion to sinus rhythm typically occurred spontaneously or after rate-control drug therapy. Approximately 11 of 24 (50%) patients who were rechallenged had recurrent atrial arrhythmias. Clinical sequelae, including stroke, have been reported in members who experienced atrial arrhythmias while receiving oprelvekin.

Children: A safe and effective dose of oprelvekin has not been established in children.

CNS effects: Stroke has been reported in the setting of members who develop atrial fibrillation/flutter while receiving oprelvekin. Members with a history of stroke or transient ischemic attack also may be at increased risk for these reactions.

Dilutional anemia: Moderate decreases in hemoglobin concentration, hematocrit, and red blood cell count (approximately 10% to 15%) without a decrease in red blood cell mass have been observed. These changes are predominantly because of an increase in plasma volume (dilutional anemia) that is primarily related to renal sodium and water retention. The decrease in hemoglobin concentration typically begins within 3 to 5 days of the initiation of oprelvekin and is reversible over approximately a week following discontinuation of oprelvekin.

Fluid retention: Oprelvekin is known to cause serious fluid retention that can result in peripheral edema, dyspnea on exertion, pulmonary edema, capillary leak syndrome, atrial arrhythmias, and exacerbation of preexisting pleural effusions. Severe fluid retention, some cases resulting in death, was reported following recent bone marrow transplantation in members who have received oprelvekin. Use with caution in members with clinically evident congestive heart failure, members receiving aggressive hydration, members who may be susceptible to developing congestive heart failure, members with a history of heart failure who are well compensated and receiving appropriate medical therapy, and members who may develop fluid retention as a result of associated medical conditions or whose medical condition may be exacerbated by fluid retention. In the postmarketing setting, ventricular arrhythmias have been reported, generally occurring within 2 to 7 days of initiation of treatment.

Myeloablative chemotherapy: Oprelvekin is not indicated following myeloablative chemotherapy. In a randomized, placebo-controlled, phase 2 study the efficacy of oprelvekin was not demonstrated. In this study, a statistically significant increased incidence in edema, conjunctival bleeding, hypotension, and tachycardia was observed in patients receiving oprelvekin as compared with placebo.

Papilledema: Papilledema has been reported in 10 of 405 (2%) members receiving oprelvekin in clinical trials following repeated cycles of exposure. The incidence was higher (16% [7/43]) in children than in adults (1% [3/362]). Nonhuman primates treated with oprelvekin at a dose of 1,000 mcg/kg subcutaneously once daily for 4 to 13 weeks developed papilledema that was not associated with inflammation or any other histologic abnormality and was reversible after dosing was discontinued. Use oprelvekin with caution in members with preexisting papilledema, or with tumors involving the CNS because it is possible that papilledema could worsen or develop during treatment. Changes in visual acuity and/or visual field defects ranging from blurred vision to blindness can occur in members with papilledema taking oprelvekin.

The following severe or fatal adverse reactions have been reported in postmarketing use in members who received oprelvekin following bone marrow transplantation: fluid retention or overload (e.g., facial edema, pulmonary edema), capillary leak syndrome, pleural and pericardial effusion, papilledema, and renal failure.

The mechanism for induction of arrhythmias is not known. Oprelvekin was not directly arrhythmogenic in animal models. In some members, development of atrial arrhythmias may be because of increased plasma volume associated with fluid retention.

BILLING/CODING INFORMATION:

The following codes may be used to report Oprelvekin:

HCPCS Coding:

J2355

injection, oprelvekin, 5 mg

ICD-10 Diagnoses Codes That Support Medical Necessity: (Effective 10/01/15)

C00.0 – C44.9

Malignant neoplasm of lip, base of tongue, gum, floor of mouth, palate, parotid gland, salivary glands, tonsil, oropharynx, nasopharynx, pyriform sinus, hypopharynx, esophagus, stomach, small intestine, colon, rectosigmoid junction, rectum, anus and anal canal, liver and intrahepatic bile ducts, gallbladder, biliary tract, pancreas, other digestive organs, nasal cavity and middle ear, accessory sinuses, larynx, trachea, bronchus and lung thymus, heart, mediastinum and pleura, respiratory system, bone and articular cartilage of limbs, skin, and merkel cell carcinoma

C46.0 – C46.9

Kaposi’s sarcoma

C48.0 – C75.9

Malignant neoplasm of retroperitoneum and peritoneum, other connective and soft tissue, nipple and areola, vulva, vagina, cervix uteri, corpus uteri, unspecified uterus, ovary, other unspecified female genital organs, placenta, penis, prostate, testis, other unspecified male genital organs, kidney, renal pelvis, ureter, bladder, other unspecified urinary organs, eye and adnexa, meninges, brain, spinal cord, cranial nerves and other parts of CNS, thyroid gland, adrenal gland and other endocrine glands and related structures

C76.0 – C85.99

Malignant neoplasm of and ill-defined sites, secondary malignant neoplasm of lymph nodes, respiratory and digestive organs, unspecified sites, Hodgkin lymphoma, follicular lymphoma, non-follicular lymphoma, mature T/NK-cell lymphomas, other and unspecified types of non-Hodgkin lymphoma

C88.0 – C91.92

Malignant immunoproliferative diseases and certain other B-cell lymphomas, multiple myeloma and malignant plasma cell neoplasms and lymphoid leukemia

C96 – C96.9

Other and unspecified malignant neoplasms of lymphoid, hematopoietic and related tissue

D03.0 – D03.9

Melanoma in situ

G73.1

Lambert-Eaton syndrome

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Part D: BCBSF has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline.

Medicare Advantage Products:

No National Coverage Determination (NCD) was found at the time of the last guideline revised date.

The following Local Coverage Determination (LCD) located at www.fcso.com was reviewed on the last guideline revised date:

• Oprelvekin (Neumega®), (L33926)

DEFINITIONS:

Microliter: equivalent to cubic millimeter.

Myeloablative chemotherapy: High dose chemotherapy which may result in the need for a bone marrow, peripheral stem cell, or a cord blood transplant in order to restore continuous production of undamaged or non-malignant blood cells.

Non-myeloid malignancy: A cancer of the body that is not associated with cancer of the white blood cells in the bone marrow, spleen or blood.

Thrombocytopenia: A decrease in platelet count, which may lead to interference with the normal clotting process and increase the risk for bleeding.

RELATED GUIDELINES:

Eltrombopag (Promacta®) Tablets, 09-J1000-13

Romiplostim Injection (Nplate™), 09-J0000-88

OTHER:

None applicable.

REFERENCES:

  1. Aribi A, Kantarjian H, Koller C, Thomas D, Faderl S, Garcia-Manero G, Cortes J. The effect of interleukin 11 on thrombocytopenia associated with tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia. Cancer. 2008 Jul 15.
  2. Bibliography: Interleukin-11 and bone marrow transplantation or hematopoietic stem cell mobilization (MEDLINE 1996 – Jan. 2000), Wyeth-Ayerst Pharmaceuticals, February 1, 2000.
  3. Clinical Pharmacology. Copyright© 2013 Elsevier. Accessed 03/06/13.
  4. DRUGDEX®. Accessed 04/13/12.
  5. Facts & Comparisons® e Answers. ©2013 Wolters Kluwer Health. Accessed 03/06/13.
  6. FDA Licensure of Neumega to Prevent Severe Chemotherapy-Induced Thrombocytopenia. Stem Cells 1998;16 (suppl 2):207-223 AlphaMed Press.
  7. Herrlinger KR, Witthoeft T, Roedler A, Bokemeyer B, Krummenerl T, Schulzke JD, Boerner N, Kueppers B, Emmrich J, Mescheder A, Schwertschiag U, Shapiro M, Stange EF. Randomized, double blind controlled trial os subcutaneous recombinant human interleukin-11 versus prednisolone in active Crohn’s disease. Am J Gastroenterol. 2006 Apr;101(4):793-7.
  8. Ingenex, HCPCS Level II Coding, 2012 Expert.
  9. Ingenex, ICD-9-CM Codes for Physicians-Volumes 1&2, Expert, 2012.
  10. Kaushansky, K. Thrombopoietin. N Engl J Med 1998:339 (11); 746-754.
  11. Mauch, P et al: Hematopoietic stem cells in the blood after stem cell factor and interleukin-11 administration: Evidence for different mechanisms of mobilization. Blood 86: 4674-4680, 1995.
  12. Micromedex® 2.0, ©2013 Truven Health Analytics Inc. Accessed 03/06/13.
  13. Montero AJ, Estrov Z, Freireich EJ, Khouri IF, Koller CA, Kurzrock R. Phase II study of low-dose interleukin-11 in patients with myelodysplastic syndrome. Leuk Lymphoma. 2006 Oct;47(10):1999-2001.
  14. Neumega® Prescribing Information. Revised 01/2011.
  15. Peeters K, Stassen JM, Collen D, Van Geet C, Freson K. Emerging treatments for thrombocytopenia: Increasing platelet production. Drug Discov Today. 2008 Jul 15.
  16. Ragni MV, Jankowitz RC, Chapman HI, Merricks EP, Kloos MT, Dillow AM, Nichols TC. A phase II prospective open-label escalating dose trial of recombinant interleukin-11 in mild von Willebrand disease. Haemophilia 2008 Aug 1.
  17. Tepler, I et al: A Randomized placebo-controlled trial of recombinant human interleukin-11 to prevent chemotherapy-induced thrombocytopenia in patients with breast cancer receiving dose-intensive cyclophosphamide and doxurubicin. J Clin Oncol 15(11): 3368-3377, 1997.
  18. The Formulary, February 1999. Pharmacy and Therapeutics Review, 1998 Updated Evaluation: Oprelvekin.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 04/10/13.

GUIDELINE UPDATE INFORMATION:

11/15/00

New Medical Coverage Guideline.

12/15/02

Reviewed with no revisions.

05/15/05

Reviewed with revisions to WHEN SERVICES ARE COVERED, added definitions, updated WHEN SERVICES ARE NOT COVERED, updated ICD-9 codes, reimbursement information and references.

07/01/06

Updated MCG number from 09-A9140-12 to 09-J0000-63.

09/15/06

Biennial review, updated references.

01/01/07

MCG revised to include Medicare Part D as a program exception.

09/15/07

Review and revision to guideline; consisting of reformatting guideline, updated ICD-9 coding, and updated references.

09/15/08

Review and revision to guideline; consisting of updating “Description” section, adding boxed warning under “Precautions” section and updating references.

08/15/09

Review and revision of guideline; consisting of updating precautions, related MCG and reference section.

06/15/10

Review and revision to guideline; consisting of updating references.

10/01/10

Revision to guideline; consisting of updating codes.

06/15/11

Review and revision to guideline; consisting of updating dosage section, ICD-10 codes and references.

06/15/12

Review and revision to guideline; consisting of updating position statement and references.

05/15/13

No Longer Review

10/01/15

Revision consisting of update to Program Exceptions section.

11/01/15

Revision: ICD-9 Codes deleted.

Date Printed: August 18, 2017: 07:55 PM