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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-J0000-84

Original Effective Date: 01/01/09

Reviewed: 12/14/16

Revised: 01/15/17

Subject: Azacitidine (Vidaza®) 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:

Azacitidine (Vidaza®) is a pyrimidine nucleoside analog of cytidine (nucleoside metabolic inhibitor). Azacitidine is believed to exert its antineoplastic effects by causing hypomethylation of DNA and direct cytotoxicity on abnormal hematopoietic cells in the bone marrow. Azacitidine is used for the treatment of myelodysplastic syndrome (MDS) and is designated an orphan drug by the US Food and Drug Administration (FDA) for use in this condition. The drug is indicated for use in individuals with the following French-American-British (FAB) subtypes of MDS: refractory anemia (RA) or RA with ringed sideroblasts (RARS) if requiring blood transfusions or accompanied by neutropenia or thrombocytopenia, RA with excess blasts (RAEB), RAEB in transformation (RAEB-T) and chronic myelomonocytic leukemia (CMMoL).

Because MDS affects the bone marrow, it is staged differently than other types of cancer. There are various classification systems used to stage MDS including the International Prognostic Scoring System (IPSS), the Revised International Prognostic Scoring System (IPSS-R), and the World Health Organization (WHO) based prognostic scoring system (WPSS). The IPSS evaluates three components when determining an overall score of 0 to 2.5: percent marrow blasts, cytogenetics (e.g., del(5)q chromosome), and cytopenias. An IPSS score of 0 corresponds to low risk, 0.5-1 to intermediate risk 1, 1.5-2 to intermediate risk 2, and 2.5 or greater to high risk. The IPSS-R stratifies individuals into 1 of 5 risk groups and is a revised version of the IPSS. The IPSS-R includes more detailed cytogenetic subgroups, separate subgroups of the percent marrow blasts, and defined measurements for hemoglobin, platelets, and neutrophil counts. The WPSS assigns individuals to 1 of 5 risk groups, and risk category may change over the course of the disease. The system is based on the WHO subtype of MDS, karyotype, and severity of anemia and individuals fall into one of the following risk groups: very low, low, intermediate, high, and very high.

Although azacitidine is not a cure for MDS, use of the drug in combination with supportive care has been shown to be superior to use of supportive care alone in improving hematologic deficits (e.g., transfusion dependence) in individuals with MDS. In individuals with high-risk MDS, improved response rates and improved survival have been reported with azacitidine therapy compared with conventional care. National Comprehensive Cancer Network Clinical Practice Guidelines for MDS indicate that all individuals with MDS should receive relevant supportive care and recommend that additional treatment is based on stratification according to clinically significant cytopenia(s) into two major risk groups: 1) relative lower-risk individuals and 2) higher-risk individuals. Those deemed lower risk have a low or intermediate-1 category International Prognostic Scoring System (IPSS), Revised International Prognostic Scoring System (IPSS-R) very low, low, or intermediate category, or WHO-classification based prognostic scoring system (WPSS) very low, low, or intermediate category. Individuals classified as high risk has an Intermediate-2/High IPSS, intermediate, high, or very high IPSS-R, or WPSS high or very high category. IPSS-R intermediate patients may be managed as very low/low risk or high/very high risk depending on additional prognostic factors such as age, performance status, serum ferritin levels, and serum lactate dehydrogenase (LDH) levels. Lower risk individuals can be further stratified according to chromosomal abnormalities and anemia characteristics. The NCCN guidelines also support the use of azacitidine for acute myelogenous leukemia and myeloproliferative neoplasms.

POSITION STATEMENT:

I. Initiation of azacitidine (Vidaza®) meets the definition of medical necessity when the dose does not exceed 100 mg/m2 per day and is administered for an indication listed in table 1 and ALL of the indication specific criteria are met:

Table 1

Indications and Specific Criteria

Indication

Specific Criteria

Acute Myelogenous Leukemia (AML)

When used in ANY of the following settings:

1. Induction (first-line) therapy as a single agent in a member 60 years of age or older

2. Post-remission therapy as a single agent in a member 60 years of age or older

3. Maintenance therapy following complete response to cytarabine therapy as a single agent in a member 60 years of age or older

4. For relapsed or refractory disease as a single agent

5. For relapsed or refractory disease in combination with sorafenib (Nexavar) AND member has a positive FLT3-ITD mutation

Myelodysplastic Syndrome (MDS)

High Risk MDS

In ANY of the following situations:

1. Member is not a transplant candidate

2. Member has not responded to or relapsed after allogeneic hematopoietic stem cell transplant

3. Member is a candidate for transplant AND is waiting for a donor or improved status

Low Risk MDS

(i.e., IPSS low and intermediate-1 categories; IPSS-R: Very low, low, intermediate categories; WPSS Very low, low, and intermediate categories)

In ANY of the following situations:

1. Use is for initial treatment AND member meets ONE of the following:

a. Member has clinically relevant thrombocytopenia

b. Member has clinically relevant neutropenia

c. Member has increased marrow blasts

d. Member has symptomatic anemia AND all of the following:

i. No deletion 5q chromosomal abnormality

ii. Serum erythropoietin greater than 500 mU/mL

iii. Low probability of response to immunosuppressive therapy

2. Member has symptomatic anemia AND all of the following:

a. Serum erythropoietin level of 500 mU/mL or less

b. Member has tried and failed erythropoietin therapy both alone and in combination with lenalidomide

c. Member has tried and failed (or not tolerated) immunosuppressive therapy

3. Member has a deletion 5q chromosomal abnormality AND all of the following:

a. Symptomatic anemia

b. Serum erythropoietin level greater than 500 mU/mL

c. Member has tried and failed, or has a contraindication to, lenalidomide

d. Member has a low probability of response to immunosuppressive therapy

Myeloproliferative Neoplasms

Primary Myelofibrosis (MF)

Post-polycythemia vera MF (Post-PV-MF)

Post-essential thrombocythemia MF (Post-EV-MF)

In EITHER of the following situations:

1. Treatment of MF-accelerated phase

2. Treatment of MF-blast phase/AML

IPSS, International Prognostic Scoring System (IPSS); Revised International Prognostic Scoring System (IPSS-R); WPSS, World Health Organization based prognostic scoring system.

Approval duration: 180 days (all indications)

II.Continuation of azacitidine (Vidaza®) meets the definition of medical necessity for the indications in Table 1 when the following criteria are met:

A. The member has experienced a beneficial response to treatment

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

C. The dose does not exceed 100 mg/m2 per day

Approval duration: 1 year

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:

Dose Adjustments:

Drug Availability: Azacitidine is supplied as a 100 mg single-use vial.

PRECAUTIONS:

CONTRAINDICATION

WARNINGS AND PRECAUTIONS

BILLING/CODING INFORMATION:

HCPCS Coding:

J9025

Injection, Azacitidine, 1 mg

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

C92.00 – C92.02

Acute myeloblastic leukemia

C92.10 – C92.12

Chronic myeloid leukemia, BCR/ABL-positive

C92.40 – C92.42

Acute promyelocytic leukemia

C92.50 – C92.52

Acute myelomonocytic leukemia

C92.60 – C92.62

Acute myeloid leukemia with 11q23-abnormality

C92.90 – C92.92

Myeloid leukemia, unspecified

C92.A0 – C92.A2

Acute myeloid leukemia with multilineage dysplasia

C92.Z0 – C92.Z2

Other myeloid leukemia

C93.00 – C93.02

Acute monoblastic/monocytic leukemia

C93.10 – C93.12

Chronic myelomonocytic leukemia

C93.90 – C93.92

Monocytic leukemia, unspecified

C94.00 – C94.02

Acute erythroid leukemia

C94.20 – C94.22

Acute megakaryoblastic leukemia

C94.40 – C94.42

Acute panmyelosis with myelofibrosis

C94.6

Myelodysplastic disease, not classified

D46.0

Refractory anemia without ring sideroblasts, so stated

D46.1

Refractory anemia with ring sideroblasts

D46.20 – D46.22

Refractory anemia with excess of blasts

D46.4

Refractory anemia, unspecified

D46.9

Myelodysplastic syndrome, unspecified

D46.A

Refractory cytopenia with multilineage dysplasia

D46.B

Refractory cytopenia with multilineage dysplasia and ring sideroblasts

D46.C

Myelodysplastic syndrome with isolated del(5q) chromosomal abnormality

D46.Z

Other myelodysplastic syndromes

D47.1

Chronic myeloproliferative disease

D47.4

Essential (hemorrhagic) thrombocythemia

D75.81

Myelofibrosis

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) was found at the time of the last guideline revised date. The following Local Coverage Determination (LCD) was reviewed on the last guideline revised date: Azacitidine (Vidaza), (L33266) located at fcso.com

DEFINITIONS:

Consolidation therapy: treatment given after cancer has disappeared following initial therapy. Consolidation therapy is used to kill any cancer cells that may be left in the body. It may include radiation therapy, a stem cell transplant, or treatment with agents that kill cancer cells. It is also called intensification therapy and postremission therapy.

FLT3-ITD mutation – a mutation of the FMS-like tyrosine kinase 3 (FLT3) gene that includes internal tandem duplication (ITDs). ITDs of the FLT3 gene are present in approximately 30% of individuals with acute myeloid leukemia and are associated with a poor prognosis.

Myelodysplastic Syndrome (MDS): any of a group of related bone marrow disorders of varying duration preceding the development of overt acute myelogenous leukemia; they are characterized by abnormal hematopoietic stem cells, anemia, neutropenia and thrombocytopenia. Also called releukemia.

Sideroblasts: a normoblast that contains granules of iron in the form of ferritin in its cytoplasm and stains with Prussian blue. A ringed sideroblast is an abnormal sideroblast containing many iron granules in its mitochondria in a ring shape around the periphery of the nucleus.

Induction Therapy: initial treatment used to reduce cancer. Induction therapy is followed by other treatments, such as chemotherapy, radiation therapy, and hormone therapy to eliminate the cancer that remains. Also called first-line therapy, primary therapy, and primary treatment.

International Prognostic Scoring System (IPSS): classification system used in staging individuals with MDS. The IPSS evaluates three components when determining an overall score of 0 to 2.5: percent marrow blasts, cytogenics (e.g., del(5)q chromosome), and cytopenias. An IPSS score of 0 corresponds to low risk, 0.5-1 to intermediate risk 1, 1.5-2 to intermediate risk 2, and 2.5 or greater to high risk.

IPSS Classification System

Risk Level

IPSS Score

Low risk

0

Intermediate risk 1

0.5-1

Intermediate risk 2

1.5-2

High risk

2.5 or greater

The following factors are used to calculate the IPSS score

 

0

0.5

1.0

1.5

2.0

% Marrow Blasts

Less than 5

5-10

 

11-20

21-30

Cytogenetics

Normal, -Y, del(5)g alone, del(20)q alone

Other

-7, del (7)q, 3 or more abnormalities

 

 

Cytopenias

• Hemoglobin <10 g/dL

Neutrophil count less than 1800/mcL

• Platelet count less than 100,000 cells/mm3

Only 1

Two of the three

 

 

 

ANC, absolute neutrophil count

Revised International Prognostic Scoring System (IPSS-R): classification system used in staging individuals with MDS. Individuals are assigned to 1 of 5 risk groups.

IPSS-R Classification System

Risk Level

IPSS-R Score

Very Low

<1.5

Low

>1.5- <3

Intermediate

>3 - <4.5

High

>4.5 - <6

Very High

>6

The following factors are used to calculate the IPSS-R score

  Prognostic variable

0

0.5

1

1.5

2

3

4

Cytogenetics

Very good

-

Good

-

Intermediate

Poor

Very poor

% Marrow Blasts

<2

-

>2 - <5

-

5-10

>10

-

Hemoglobin

>10

-

8 - <10

< 8

     

Platelets

>100

50 - <100

<50

-

-

-

-

ANC

>0.8

<0.8

-

-

-

-

-

ANC, absolute neutrophil count

World Health Organization (WHO) Prognostic Scoring System (WPSS): classification system used in staging individuals with MDS. This system is based on the WHO classification of the MDS subtype, karyotype, and presence of severe anemia. Individuals are assigned to 1 of 5 risk groups and the risk category may change over the course of the disease.

WPSS Classification System

 

Score

Variable

0

1

2

3

WHO Category

RCUD, RARS, MDS with isolated del (5q)

RCMD

RAEB-1

RAEB-2

Karyotype

Good

Intermediate

Poor

--

Severe anemia (hemoglobin <9 g/dL in males or <8 g/dL in females)

Absent

Present

--

--

RCUD, refractory cytopenia with unilineage dysplasia (includes refractory anemia, refractory neutropenia, and refractory thrombocytopenia); RAEB, refractory anemia with excess blasts; RARS, refractory anemia with ringed sideroblasts; RCMD, refractory cytopenia with multilineage dysplasia; A score of 0=very low risk, 1= low risk, 2=intermediate risk, 3-4=high risk, 5-6=very high risk

RELATED GUIDELINES:

Oprelvekin; Interleukin 11 (Neumega®), 09-J0000-63
Lenalidomide (Revlimid®), 09-J0000-80

Carboplatin (Paraplatin®) IV, 09-J0000-93

Docetaxel (Taxotere®) IV, 09-J0000-95

Romiplostim Injection (Nplate™), 09-J0000-98

OTHER:

None applicable.

REFERENCES:

  1. AHFS Drug Information. Bethesda (MD): American Society of Health-System Pharmacists, Inc; 2016 [cited 2016 Nov 21]. In: STAT!Ref Online Electronic Medical Library [Internet]. Available from: http://online.statref.com/.
  2. Celgene. Vidaza (azacitidine) injection, August 2016 [cited 2016 Nov 21]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3495a71a-cc04-4776-851f-f185956f32af /.
  3. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2016 [cited 2016 Nov 21]. Available from: http://www.clinicalpharmacology.com/.
  4. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 2016 Nov 21]. Available from: http://clinicaltrials.gov/.
  5. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2016 Nov 21]. Available from: http://www.thomsonhc.com/.
  6. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Acute Myeloid Leukemia, v. 2.2016 [cited 2016 Nov 28]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  7. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Myelodysplastic Syndromes, v. 2.2017[cited 2016 Nov 28]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  8. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Myeloproliferative Neoplasms, v. 2.2017 [cited 2016 Nov 28]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  9. NCCN Drugs & Biologics Compendium [Internet]. Fort Washington (PA): National Comprehensive Cancer Network; 2016 [cited 2016 Nov 28]. Available from: http://www.nccn.org/professionals/drug_compendium/content/contents.asp/.
  10. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2016 [cited 2016 Nov 28]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Coverage Committee on 12/14/16.

GUIDELINE UPDATE INFORMATION:

01/01/09

New Medical Coverage Guideline.

01/15/10

Review and revision to guideline; consisting of adding acute myeloid leukemia as a covered indication.

01/15/11

Review and revision to guideline; consisting of updating coding, related guidelines and references.

08/17/11

Revision; ICD-10 codes updated.

01/15/12

Review and revision to guideline; consisting of revising position statement, precautions, codes and references.

01/15/13

Review and revision to guideline; consisting of revising and reformatting position statement and adding AML as covered indication; reformatting/revising description, dosage/administration, precaution sections; updating references and coding; added definitions.

01/15/14

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

01/15/15

Review and revision to guideline; consisting of position statement, dosage/administration; precautions/warnings, coding, references.

10/01/15

Revision to guideline consisting of coding updates and update to Program Exceptions section.

11/01/15

Revision: ICD-9 Codes deleted.

1/15/16

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

01/15/17

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

Date Printed: June 23, 2017: 06:20 PM