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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-J1000-63

Original Effective Date: 03/15/12

Reviewed: 02/08/17

Revised: 05/15/17

Next Review: 02/14/18

Subject: Ruxolitinib (Jakafi™) Tablets

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:

Myelofibrosis, a myeloproliferative neoplasm, can present as a primary disease or can evolve from polycythemia vera or essential thrombocytopenia. It is characterized by marrow fibrosis, progressive anemia, and extramedullary hematopoiesis and manifests primarily as splenomegaly. Myelofibrosis manifests as debilitating symptoms (e.g., fatigue, weakness, abdominal pain, cachexia, weight loss, pruritus, night sweats, and bone pain), which are thought to be the combined effects of massive splenomegaly and elevated levels of proinflammatory cytokines. Traditional therapeutic options, including splenectomy, have demonstrated only limited benefit and although allogeneic stem-cell transplant may cure myelofibrosis, few individuals are eligible for this treatment. It is hypothesized that the pathogenesis of myelofibrosis is related to direct or indirect activation of the intracellular Janus kinase (JAK) signal transducer and activator transcription (STAT) pathway. Additionally, proinflammatory cytokines that play an important role in myelofibrosis signal through JAK 1 (JAK1) AND JAK2.

Ruxolitinib (Jakafi™), a potent and selective inhibitor of JAK1 and JAK2, was approved by the US Food and Drug Administration (FDA) in November 2011 for the treatment of intermediate- or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. The approval was based principally on the results of two pivotal clinical trials, COMFORT-I and COMFORT-II, in which ruxolitinib was compared to placebo or best available therapy. The primary endpoint for each study was the proportion of subjects with a reduction of 35% or more in spleen volume as measured by means of magnetic resonance imaging or computed tomography. Overall survival was assessed, but was a secondary endpoint. In both studies, significantly more subjects treated with ruxolitinib achieved the primary endpoint when compared to subjects treated with placebo or best available therapy. For the secondary endpoint of overall survival, at the time of data cutoff, there was no significant difference between ruxolitinib and placebo or best available therapy in either trial; however, in COMFORT-I, a survival analysis based on a planned data cutoff with 4 additional months of follow-up revealed a significant survival advantage for subjects in the ruxolitinib arm (HR=0.50, CI 0.25 to 0.98, p=0.04). Additional studies are required to determine the effect of ruxolitinib on disease progression and survival.

National Comprehensive Cancer Network (NCCN) guidelines for the treatment of myeloproliferative disorders recommend the use of ruxolitinib for primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis.

POSITION STATEMENT:

Comparative Effectiveness

The Food and Drug Administration 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, or emergency facility is not considered medically necessary.

I. Initiation of ruxolitinib (Jakafi™) meets the definition of medical necessity for members diagnosed with ANY of the following conditions when ALL associated criteria are met:

1. Primary myelofibrosis (MF), post-polycythemia vera myelofibrosis (Post-PV-MF), or post-essential thrombocythemia myelofibrosis (Post-ET-MF)

a. Member meets ONE of the following:

i. Disease is classified as intermediate-2 or high-risk and ALL of the following:

1. Member is not a transplant candidate

2. Platelets are greater than 50,000

ii. Ruxolitinib is used for improvement of clinical symptoms and disease is classified as ONE of the following:

1. Low risk or intermediate-1

2. MF accelerated phase

3. MF blast phase/AML

b. Dose does not exceed 50 mg/day using the fewest number of tablets per day

2. Polycythemia vera

a. Member has a contraindication or inadequate response to hydroxyurea

b. Dose does not exceed 50 mg/day using the fewest number of tablets per day

Approval duration: 180 days

II. Ruxolitinib meets the definition of medical necessity when used for the following designated Orphan Drug indications (http://www.fda.gov/orphan/designat/list.htm) when the dose does not exceed the maximum FDA-approved dose:

1. Pancreatic cancer

2. Graft versus host disease

Approval duration: 180 days

III. Continuation of ruxolitinib (Jakafi™) meets the definition of medical necessity for MF, Post-PV-MF, Post-ET-MF, polycythemia vera and orphan indications 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, OR the member has previously met all indication-specific criteria for coverage

2. The member has experienced a beneficial response to therapy (e.g., reduction in spleen size, improvement in clinical symptoms)

3. The dose does not exceed 50 mg/day using the fewest number of tablets per day

Approval duration: 180 days

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

• Myelofibrosis - The starting dose is based on baseline platelet count:

o Greater than 200 X 109/L: 20 mg given orally twice daily

o 100 X 109/L to 200 X 109/L: 15 mg given orally twice daily

o 50 X 109/L to less than 100 X 109/L: 5 mg given orally twice daily

o May titrate up to 50 mg/day

• Polycythemia Vera

o 10 mg given orally twice daily

o May titrate up to 50 mg/day

Dose Adjustments

Refer to prescribing information.

Drug Availability

Ruxolitinib is available as tablet in the following strengths: 5-, 10-, 15-, 20-, and 25 mg.

PRECAUTIONS:

Hematologic effects: Treatment with ruxolitinib can cause hematologic adverse reactions, including thrombocytopenia, anemia, and neutropenia. Members with platelet counts of less than 200,000 at the start of therapy are more likely to develop thrombocytopenia during treatment. In clinical trials, thrombocytopenia was generally reversible and was usually managed by reducing the dose or temporarily withholding ruxolitinib. If clinically indicated, platelet transfusions may be administered. Monitor CBC prior to therapy initiation and as clinically indicated throughout therapy; adjust dose as required.

Infections: Assess members for the risk of developing serious bacterial, mycobacterial, fungal, and viral infections. Resolve active serious infections before starting therapy with ruxolitinib. Carefully observe members receiving ruxolitinib for signs and symptoms of infection and initiate appropriate treatment promptly.

Herpes zoster: Inform members about early signs and symptoms of herpes zoster and advise members to seek treatment as early as possible.

Progressive multifocal leukoencephalopathy (PML): PML has been reported with ruxolitinib treatment for myelofibrosis. If PML is suspected, discontinue ruxolitinib and evaluate.

Tuberculosis: infection has been reported. Observe patients for signs and symptoms of active tuberculosis and manage promptly.

Hepatitis B: viral load increases have been reported in patients with chronic hepatitis B virus.

Symptom Exacerbation Following Interruption or Discontinuation: Following discontinuation, symptoms from myeloproliferative neoplasms may return to pretreatment levels over a period of approximately one week. Some patients with myelofibrosis have experienced one or more of the following adverse events: fever, respiratory distress, hypotension, DIC, or multi-organ failure. Manage with supportive care and consider resuming treatment.

Lipid elevations: Assess lipid levels 8-12 weeks from start of therapy and treat as needed.

Risk of Non-Melanoma Skin Cancer: basal cell, squamous cell, and Merkel cell carcinoma have occurred. Perform periodic skin examinations.

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding:

C9399

Unclassified drugs or biologicals

J8999

Prescription drug, oral, chemotherapeutic, NOS

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

C25.0 – C25.9

Malignant neoplasm of pancreas

C94.40 – C94.42

Acute panmyelosis with myelofibrosis

C94.6

Myelodysplastic disease, not classified

D45

Polycythemia vera

D47.1

Chronic myeloproliferative disease

D47.4

Osteomyelofibrosis

D75.81

Myelofibrosis

D89.810 – D89.813

Graft-versus-host disease

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 revised date.

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

DEFINITIONS:

Essential thrombocythemia: an increased number of thrombocytes (platelets) in the blood, without a known cause. Also called essential thrombocytosis.

International Prognostic Scoring System for myelofibrosis: mechanism for assessing a member’s prognosis at the time of diagnosis; assigns a value of 1 for each prognostic factor (Table 4). A score of 0 is indicative of low risk, 1 is indicative of intermediate-1 risk, 2 intermediate-2 risk, and 3 or more points is indicative of high risk. The risk group corresponds to a median overall survival that ranges from 2.25 years (high risk) to 11.25 years (low risk); Individuals classified as intermediate-1 or intermediate-2 have an estimated median survival of 7.92 and 4 years, respectively.

Table 1

Prognostic factors

IPSS Risk Factors

Age greater than 65

WBC greater than 25,000

Hemoglobin less than 10 g/dL

Peripheral blood blasts 1% or greater

Constitutional symptoms

Myelofibrosis: myeloproliferative disease in which the proliferation of an abnormal type of bone marrow stem cell results in fibrosis, or the replacement of the marrow with collagenous connective tissue fibers.

Polycythemia vera: A disease in which there are too many red blood cells in the bone marrow and blood, causing the blood to thicken. The number of white blood cells and platelets may also increase. The extra blood cells may collect in the spleen and cause it to become enlarged. They may also cause bleeding problems and make clots form in blood vessels.

Primary myelofibrosis: a progressive, chronic disease in which the bone marrow is replaced by fibrous tissue and blood is made in organs such as the liver and the spleen, instead of the bone marrow. This disease is marked by an enlarged spleen and progressive anemia. Also called agnogenic myeloid metaplasia, chronic idiopathic myelofibrosis, idiopathic myelofibrosis, and myelosclerosis with myeloid metaplasia.

Splenomegaly: enlarged spleen.

RELATED GUIDELINES:

Erythropoiesis Stimulating Agents, 09-J0000-31
Granulocyte Colony Stimulating Factors, 09-J0000-62

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

OTHER:

None

REFERENCES:

  1. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2017 [cited 2017 Jan 18]. Available from: http://www.clinicalpharmacology.com/.
  2. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 2015 Jan 3]. Available from: http://clinicaltrials.gov/.
  3. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2017 Jan 18]. Available from: http://www.thomsonhc.com/.
  4. Incyte. Jakafi (ruxolitinib) tablets. 2017 [cited 2017 Jan 18]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f1c82580-87ae-11e0-bc84-0002a5d5c51b/.
  5. NCCN Drugs & Biologics Compendium [Internet]. Fort Washington (PA): National Comprehensive Cancer Network; 2017 [cited 2017 Jan 23]. Available from: http://www.nccn.org/professionals/drug_compendium/content/contents.asp/.
  6. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Myeloproliferative Neoplasms, v. 2.2017 [cited 2017 Jan 23]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  7. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2017 [cited 2017 Jan 18]. 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 Policy Committee on 02/08/17.

GUIDELINE UPDATE INFORMATION:

03/15/12

New Medical Coverage Guideline.

03/15/13

Review and revision to guideline; consisting of revising/reformatting position statement to strengthen medical necessity criteria; revised/reformatted/updated description, dosage/administration, precautions sections; updated references; added pertinent definitions.

11/15/13

Revision to guideline; consisting of adding approval duration and updating dosage/administration section.

03/15/14

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

03/15/15

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

11/01/15

Revision: ICD-9 Codes deleted.

03/15/16

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

05/15/16

Revision to guideline; consisting of updating position statement.

03/15/17

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

05/15/17

Revision to guideline; consisting of updating the position statement.

Date Printed: June 26, 2017: 11:44 AM