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Date Printed: June 26, 2017: 01:24 AM

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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-J1000-87

Original Effective Date: 03/15/13

Reviewed: 02/08/17

Revised: 03/15/17

Subject: Omacetaxine Mepesuccinate (Synribo®) Injection

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:

Omacetaxine mepesuccinate (Synribo®) is a cephalotaxine ester that inhibits protein synthesis by binding to the A-site in the peptidyl-transferase center of the large ribosomal subunit. It reduces protein levels of Bcr-Abl and Mcl-1 independent of direct Bcr-Abl binding. Omacetaxine was given orphan designation status for the treatment of chronic myelogenous leukemia (CML) in 2006 and was subsequently approved by the FDA in October 2012 for treatment of chronic phase (CP) or accelerated phase (AP) chronic myeloid leukemia (CML) that is resistant and/or intolerant to two or more tyrosine kinase inhibitors (TKI). In a pooled analysis of two studies, treatment with omacetaxine resulted in a major cytogenetic response rate of 18.4% in patients with CP-CML (n = 76) and a complete hematologic response rate or no evidence of leukemia (composite endpoint) of 14.3% in patients with AP-CML (n = 35). Omacetaxine has demonstrated efficacy in CML patients with the T315I mutation who had failed previous TKI therapy in a phase II study (n = 62). In May 2014, the FDA approved revised labeling to include home administration in patients appropriate for self-administration or for administration by a caregiver.

Chronic myelogenous leukemia (CML) is a hematopoietic stem cell disease characterized by a reciprocal translocation between chromosomes 9 and 22, resulting in the formation of the Philadelphia (Ph) chromosome. CML occurs in three different phases (chronic, accelerated, and blast phase) and is usually diagnosed in the chronic phase. The median age of disease onset is 67 years, but CML occurs in all age groups. Untreated chronic phase CML will eventually progress to advanced phase disease in 3 to 5 years. The introduction of TKIs improved 10-year overall survival from approximately 20% to 80 to 90%. Despite positive outcomes seen with TKIs in the treatment of CML, drug resistance has been observed. One of the most common mechanisms of resistance involves point mutations in the kinase domain of BCR-ABL, which impairs the activity of TKIs, including imatinib (Gleevec®), dasatinib (Sprycel®), nilotinib (Tasigna®) and bosutinib (Bosulif®). One important mutation, the T315I, is known as the “gatekeeper” mutation, as it displays resistance to all TKIs with the exception of ponatinib (Iclusig®). Current guidelines recommend checking mutational analysis in the following situations: if there is inadequate initial response, any sign of loss of response, and in disease progression to accelerate-phase or blast-phase CML (CML-AP and CML-BP, respectively).

POSITION STATEMENT:

Comparative Effectiveness

The FDA has deemed the drug(s) or biological product(s) in this coverage policy to be appropriate for self-administration or administration by a caregiver (i.e., not a healthcare professional). Therefore, coverage (i.e., administration) in a provider-administered setting such as an outpatient hospital, ambulatory surgical suite, physician office, or emergency facility is not considered medically necessary.

Initiation of omacetaxine mepesuccinate (Synribo®) meets the definition of medical necessity when ALL of the following criteria are met:

1. Member has a diagnosis of Philadelphia- chromosome positive (Ph+) chronic myelogenous leukemia (CML).

2. Member’s CML is in either the chronic or accelerated phase (does NOT include blast phase)

OR

The member has had a post-transplant relapse

3. Member has tested positive for the T315I BCR-ABL kinase domain mutation (lab documentation must be submitted)

OR

Member meets any of the following in reference to two or more TKI therapies (i.e., imatinib, dasatinib, nilotinib, or bosutinib)

a. Did not achieve recommended treatment goals defined by NCCN as ANY of the following:

• BCR-ABL1 transcript levels >10% or lack of partial cytogenetic response (i.e., >35% Ph-positive metaphases) at 3 or 6 months

• Lack of a complete response (i.e., Ph-positive metaphases are detectable), BCR-ABL1 transcript levels >1%, or cytogenetic relapse at 12 months

b. Had persistent intolerable adverse effects despite appropriate dose modification (the specific adverse effect must be provided)

c. Has documented genetic resistance (lab documentation must be submitted)

d. Has an FDA-labeled contraindication (the specific contraindication must be provided)

5. Member is NOT taking a TKI (i.e., imatinib, dasatinib, nilotinib, ponatinib, or bosutinib) concurrently

6. Dose does not exceed 1.25 mg/m2 (+10% to account for rounding) twice daily for 14 consecutive days every 28 days

Approval duration: 6 months

Continuation omacetaxine (Synribo®) meets the definition of medical necessity when ALL of the following criteria are met:

1. The member has been previously approved by Florida Blue or another health plan in the past 2 years for the treatment of CML, OR the member has previously met all indication-specific criteria.

2. Member’s disease has not progressed during treatment with omacetaxine.

3. Member is NOT taking a TKI (i.e., imatinib, dasatinib, nilotinib, ponatinib, or bosutinib) concurrently with omacetaxine.

4. Dosage does not exceed 1.25 mg/m2 (+10% to account for rounding) twice daily for 14 consecutive days every 28 days for members still receiving initiation therapy (i.e., hematologic response has not yet been achieved),

OR

Dosage does not exceed 1.25 mg/m2 (+10% to account for rounding) twice daily for 7 consecutive days every 28 days for members receiving maintenance therapy (i.e., hematologic response has been achieved).

Approval duration: 1 year

NOTE: Quest Diagnostics® can perform the BCR-ABL kinase domain mutation test. Current NCCN guidelines recommend checking mutational analysis in the following situations: if there is inadequate initial response, any sign of loss of response, and in disease progression to accelerate-phase or blast-phase CML (CML-AP and CML-BP, respectively).

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: omacetaxine is indicated for the treatment of adults with chronic or accelerated phase chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors. The induction dose is 1.25 mg/m2 subcutaneously twice daily for 14 days repeated every 28 days, over a 28-day cycle. Cycles should be repeated every 28 days until a hematologic response is achieved. The recommended maintenance dose is 1.25 mg/m2 subcutaneously twice daily for seven days repeated every 28 days, over a 28 day cycle. Treatment should be continued for as long as a clinical benefit is observed. In clinical trials, the median duration of therapy was 7.4 months (median of 6 treatment cycles) in patients with chronic phase CML and 1.9 months (median of 2 treatment cycles) in those with accelerated phase CML.

Before a decision is made to allow home administration ensure that the member is an appropriate candidate for self-administration or for administration by a caregiver. Provide training on proper handling, storage conditions, administration, disposal, and clean-up of accidental spillage of the product. Ensure the member receives the necessary supplies for home administration. At minimum these should include:

• Reconstituted patient-specific dose in syringe with a capped needle for subcutaneous injection

• Protective eyewear and gloves

• An appropriate biohazard container

• Absorbent pad(s) for placement of administration materials and for accidental spillage

• Alcohol swabs and gauze pads

• Ice packs or cooler for transportation of reconstituted syringes

Dose Modifications:

• Hematologic Toxicity: treatment cycles may be delayed and/or the number of days of dosing during the cycle reduced for hematologic toxicities (e.g. neutropenia, thrombocytopenia). If a patient experiences Grade 4 neutropenia (absolute neutrophil count (ANC) less than 0.5 x 109/L) or Grade 3 thrombocytopenia (platelet counts less than 50 x 109/L) during a cycle, delay starting the next cycle until ANC is greater than or equal to 1 x 109/L and platelet count is greater than or equal to 50 x 109/L. Also, for the next cycle, reduce the number of dosing days by 2 days (e.g., to 12 or 5 days).

Drug Availability: supplied as a sterile, preservative-free, single-use vial containing 3.5 mg of omacetaxine mepesuccinate as a lyophilized powder.

PRECAUTIONS:

CONTRAINDICATIONS

None

PRECAUTIONS/WARNINGS

Myelosuppression: severe and fatal thrombocytopenia, neutropenia and anemia. Monitor hematologic parameters frequently (i.e., weekly during induction and initial maintenance cycles, then every 2 weeks thereafter or as clinically indicated).

Bleeding: severe thrombocytopenia and increased risk of hemorrhage. Fatal cerebral hemorrhage and severe, non-fatal gastrointestinal hemorrhage

Hyperglycemia: glucose intolerance and hyperglycemia including hyperosmolar non-ketotic hyperglycemia

Embryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential to avoid pregnancy

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding

J9262

Injection, omacetaxine mepesuccinate, 0.01 mg

ICD-10 Diagnoses Codes That Support Medical Necessity

C92.10

Chronic myeloid leukemia, bcr/abl-positive, not having achieved remission

C92.11

Chronic myeloid leukemia, bcr/abl-positive, in remission

C92.12

Chronic myeloid leukemia, bcr/abl-positive, in relapse

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 Advantage Products: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of the last guideline review date.

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

DEFINITIONS:

Accelerated Phase CML: is a phase of chronic myelogenous leukemia in which the disease is progressing.

Blast Phase CML: is the final phase in the evolution of CML, and behaves like an acute leukemia, with rapid progression and short survival.

Chronic Phase CML: approximately 85% of members with CML are in the chronic phase at the time of diagnosis. During this phase, members are usually asymptomatic or have only mild symptoms of fatigue, left side pain, joint and/or hip pain, or abdominal fullness.

Chronic Myelogenous Leukemia (CML): also known as chronic granulocytic leukemia (CGL), is a cancer of the white blood cells. It is a form of leukemia characterized by the increased and unregulated growth of predominantly myeloid cells in the bone marrow and the accumulation of these cells in the blood.

Cytogenetic: is a branch of genetics that is concerned with the study of the structure and function of the cell, especially the chromosomes. It includes routine analysis of G-banded chromosomes, other cytogenetic banding techniques, as well as molecular cytogenetics such as fluorescent in situ hybridization (FISH) and comparative genomic hybridization (CGH).

Induction Chemotherapy: the use of drug therapy as the initial treatment for patients presenting with advanced cancer that cannot be treated by other means.

Inadequate chronic-phase CML treatment response: BCR-ABL1 transcript levels >10% or lack of partial cytogenetic response (i.e., >35% Ph-positive metaphases) at 3 or 6 months; or lack of a complete response (i.e., Ph-positive metaphases are detectable), BCR-ABL1 transcript levels >1%, or cytogenetic relapse at 12 months.

Philadelphia chromosome or Philadelphia translocation: is a specific chromosomal abnormality that is associated with chronic myelogenous leukemia (CML).

RELATED GUIDELINES:

Allogeneic Bone Marrow and Stem Cell Transplantation, 02-38240-01
Autologous Bone Marrow and Stem Cell Transplantation, 02-38241-01

Immune Globulin Therapy, 09-J0000-06

Dasatinib (Sprycel®) Tablets, 09-J1000-43

Imatinib Mesylate (Gleevec®) Tablets, 09-J1000-46

Nilotinib (Tasigna®) Capsules, 09-J1000-48

Bosutinib (Bosulif™) Tablets, 09-J1000-84

Ponatinib (Iclusig®) Tablets, 09-J1000-89

OTHER:

None applicable.

REFERENCES:

  1. Cortes J, Digumarti R, Parikh PM, et al. Phase 2 study of subcutaneous omacetaxine mepesuccinate for chronic-phase chronic myeloid leukemia patients resistant to or intolerant of tyrosine kinase inhibitors. Am J Hematol. 2013 May;88(5):350-4.
  2. Cortes JE, Kantarjian HM, Rea D, et al. Final analysis of the efficacy and safety of omacetaxine mepesuccinate in patients with chronic- or accelerated-phase chronic myeloid leukemia: Results with 24 months of follow-up. Cancer. 2015 May 15;121(10):1637-44.
  3. Cortes J, Lipton JH, Rea D, et al. Phase 2 study of subcutaneous omacetaxine mepesuccinate after TKI failure in patients with chronic-phase CML with T315I mutation. Blood. 2012 Sep 27;120(13):2573-80.
  4. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2017. Available at: www.clinicalpharmacilogy-ip.com. Accessed 1/19/17.
  5. Khoury HJ, Cortes J, Baccarani M, Wetzler M, et al. Omacetaxine mepesuccinate in patients with advanced chronic myeloid leukemia with resistance or intolerance to tyrosine kinase inhibitors. Leuk Lymphoma. 2015 Jan;56(1):120-7.
  6. Micromedex® Healthcare Series [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed 1/19/17.
  7. National Comprehensive Cancer Network. Cancer Guidelines. Cancer Guidelines and Drugs and Biologics Compendium. Accessed 1/19/17.
  8. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology Version 2.2017. Chronic Myelogenous Leukemia. Available at http://www.nccn.org/professionals/physician_gls/PDF/cml.pdf. Accessed 1/25/17.
  9. Synribo (omacetaxine mepesuccinate) [package insert]. Teva Pharmaceuticals, Inc. North Wales (PA): July 2016.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 02/08/17.

GUIDELINE UPDATE INFORMATION:

03/15/13

New Medical Coverage Guideline.

01/01/14

Revision to guideline; consisting of code update.

03/15/14

Review and revision to guideline; consisting of reformatting position statement, updated dosage/administration section, program exceptions, and references.

03/15/15

Review and revision to guideline; consisting of revising position statement and decision tree, and updating the description, dosage/administration, and references.

11/01/15

Revision: ICD-9 Codes deleted.

03/15/16

Review and revision to guideline consisting of description, position statement, definitions, and references.

03/15/17

Review and revision to guideline consisting of removal of the age requirement in the position statement, and updates to description section, definitions, and references.

Date Printed: June 26, 2017: 01:24 AM