Print

Date Printed: August 21, 2017: 07:53 PM

Private Property of Blue Cross and Blue Shield of Florida.
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-J2000-42

Original Effective Date: 08/15/15

Reviewed: 07/13/16

Revised: 08/15/16

Next Review: No Longer Scheduled for Routine Review (NLR)

Subject: Dinutuximab (Unituxin™)

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.

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

DESCRIPTION:

Dinutuximab (Unituxin™) is a chimeric monoclonal antibody that binds to the glycolipid disialoganglioside (GD2). This glycolipid is expressed on neuroblastoma cells and on normal cells of neuroectodermal origin, including the central nervous system and peripheral nerves. GD2 binding induces cell lysis of GD2-expressing cells through antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).

Dinutuximab (Unituxin™) is indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA), for the treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent, multimodality therapy.

Neuroblastoma is the most common extracranial solid tumor in childhood with 90% of cases diagnosed at younger than 5 years of age. The yearly incidence is approximately 10.54 cases per 1 million in children younger than 15 years and prevalence about 1 case per 7,000 live births. The neuroblastoma originates in the adrenal medulla or the paraspinal sites where sympathetic nervous system tissue resides. Patients commonly present with an abdominal mass and up to 70% have metastatic disease at diagnosis. Prognosis depends on patient age, site of the primary tumor, tumor histology, regional lymph node involvement, stage of disease, response to treatment, and biological features.

The Children’s Oncology Group (COG) Neuroblastoma Risk Grouping is one of the risk stratification systems used to determine treatment. The risk system is based on the patient age at diagnosis, biological characteristics of the tumor (MYCN oncogene status, histopathology classification, tumor DNA index), and stage of the tumor based on the International Neuroblastoma Stage System (INSS). Patients are classified as low, intermediate, or high risk. For patients determined to have high-risk neuroblastoma, treatment is generally divided into three phases: induction, consolidation, and maintenance. Induction therapy includes chemotherapy followed by surgical resection of the primary tumor. The consolidation phase is characterized by myeloablative chemotherapy and hematopoietic stem cell transplantation (HSCT). Radiation therapy is also performed in the consolidation phase before, during or after myeloablative therapy. Agents used in the maintenance phase include differentiating therapy (oral isotretinoin) and immunotherapy (anti-GD2 monoclonal antibody, interleukin-2/GM-CSF).

POSITION STATEMENT:

Initiation of dinutuximab (Unituxin™) meets the definition of medical necessity when ALL of the following criteria are met:

  1. Member is diagnosed with high-risk neuroblastoma
  2. Member is < 18 years of age
  3. Therapy is in combination with isotretinoin
  4. Therapy includes alternation of a granulocyte-macrophage colony-stimulating factor (sargramostim) and interleukin-2 (aldesleukin)
  5. Member demonstrated at least a partial response to multimodal therapy (chemotherapy, surgery)
  6. Dose does not exceed 70 mg/m2 every 24 days for a maximum of 5 cycles

Duration of Approval: 6 months

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.

FDA-approved

• The recommended dose of dinutuximab (Unituxin™) is 17.5 mg/m2/day administered as an infusion intravenously over 10- 20 hours for 4 consecutive days for a maximum of 5 cycles. Cycles 1, 3, and 5 are each 24 days in duration and cycles 2 and 4 are each 32 days in duration. Initiate at an infusion rate of 0.875 mg/m2/hour for 30 minutes and then gradually increase as tolerated to a maximum of 1.75 m/m2/hour.

• Verify that patients have adequate hematologic, respiratory, hepatic, and renal function prior to initiating each course of dinutuximab (Unituxin™).

• Administer required premedication and hydration prior to initiation of each infusion.

Dose Adjustments

• Manage adverse reactions by infusion interruption, infusion rate reduction (50%), dose reduction, or permanent discontinuation of dinutuximab (Unituxin™).

• Permanent discontinuation of dinutuximab (Unituxin™) is recommended for the following adverse reactions:

o Grade 3 or 4 anaphylaxis

o Grade 3 or 4 serum sickness

o Grade 3 pain unresponsive to maximum support measures

o Grade 4 sensory neuropathy or Grade 3 sensory neuropathy that interferes with daily activities for more than 2 weeks

o Grade 2 peripheral motor neuropathy

o Subtotal or total vision loss

o Grade 4 hyponatremia despite appropriate fluid management

Drug Availability

• 17.5 mg/5 mL (3.5 mg/mL) solution in a single-use vial.

PRECAUTIONS:

Boxed Warning

• SERIOUS INFUSION REACTIONS AND NEUROPATHY

Life-threatening infusion adverse reactions may occur and IV prehydration (0.9% Sodium Chloride) and premedication with antihistamines and antipyretics should be administered. Immediately interrupt for severe infusion reactions and permanently discontinue for anaphylaxis.

Severe neuropathic pain may occur and opioids should be administered prior to, during and for 2 hours following completion of the infusion. Severe peripheral sensory neuropathy ranged from 2-9% in patients with neuroblastoma, and severe motor neuropathy was observed in adults. Discontinue use for severe unresponsive pain, severe sensory neuropathy, or moderate to severe peripheral neuropathy.

Contraindications

• History of anaphylaxis to dinutuximab (Unituxin™).

Precautions/Warnings

• Capillary leak syndrome and hypotension: Administer prehydration with 0.9% Sodium Chloride IV infusion one hour prior to initiation of therapy and monitor patients closely. The infusion may require interruption, modification, or discontinuation.

• Infection: Interrupt until resolution of systemic infection.

• Neurological disorders of the Eye: Interrupt for dilated pupil with sluggish light reflex or other visual disturbances and permanently discontinue for recurrent eye disorders or loss of vision.

• Bone marrow suppression: Monitor peripheral blood counts during therapy.

• Electrolyte abnormalities: Monitor serum electrolytes closely.

• Atypical hemolytic uremic syndrome: Permanently discontinue and institute supportive management.

• Embryo-Fetal toxicity: May cause fetal harm. Advise females of reproductive potential of potential risk to a fetus and to use effective contraception.

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding

C9399

Unclassified drugs or biologicals

J9999

Not otherwise classified, antineoplastic drugs

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

C49.0 – C49.9

Malignant neoplasm of connective and soft tissue

C72.9

Malignant neoplasm of central nervous system, unspecified

C74.0 – C74.9

Malignant neoplasm of adrenal gland

C80.0

Disseminated malignant neoplasm without specification of site

C80.1

Other malignant neoplasm without specification of site

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: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of the guideline creation.

DEFINITIONS:

Partial Response in Neuroblastoma: 50 to 90% reduction of primary tumor; 50% or greater reduction in measureable sites of metastases; 0-1 bone marrow samples with tumor; number of positive bone sites decreased by greater than 50%.

RELATED GUIDELINES:

None

OTHER:

None

REFERENCES:

  1. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.;2016. URL www.clinicalpharmacilogy-ip.com. Accessed 6/16/16.
  2. Dinutuximab. In McEvoy GK, editor. AHFS drug information 2016 [monograph on the internet]. Bethesda (MD): American Society of Health-System Pharmacists; 2016 [cited 2016 June 16].
  3. Micromedex® Healthcare Series [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed 6/16/16.
  4. National Cancer Institute: Neuroblastoma. http://www.cancer.gov/types/neuroblastoma/hp/neuroblastoma-treatment-pdq#section/_1 Accessed 6/22/2015.
  5. National Cancer Institute: Partial response in neuroblastoma. http://nciterms.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&version=15.05d&code=C103313&ns=NCI_Thesaurus&key=n1442942250&b=1&n=null. Accessed 6/26/2015.
  6. Unituxin (dinutuximab) Injection. Silver Spring, MD: United Therapeutics Corp;March 2015.
  7. Yu AL, Gilman AL, Ozkaynak MF et al. Anti-GD2 Antibody with GM-CSF, Interleukin-2, and Isotretinoin for Neuroblastoma. N Engl J Med. 2010; 363: 1324-1334.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 07/13/16.

GUIDELINE UPDATE INFORMATION:

08/15/15

New Medical Coverage Guideline.

11/01/15

Revision: ICD-9 Codes deleted.

08/15/16

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

Date Printed: August 21, 2017: 07:53 PM