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This medical policy (medical coverage guideline) is Copyright 2016, 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 2016 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-J1000-18

Original Effective Date: 03/15/10

Reviewed: 02/12/14

Revised: 11/01/15

Subject: Pralatrexate (Folotyn™) IV

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:

Pralatrexate (Folotyn) is a novel antifolate that is structurally similar to methotrexate. It has been investigated as a treatment option for relapsed or refractory peripheral T-cell lymphoma (PTCL) and as a second-line option in the treatment of cutaneous T-cell lymphomas (CTCL), specifically mycosis fungoides (MF) and Sezáry syndrome (SS). In early clinical trials, the dose-limiting toxicity was stomatitis; the use of folic acid and vitamin B12 supplementation during pralatrexate therapy reduces this toxicity.

PTCL are a heterogeneous group of lymphoproliferative disorders arising from mature T-cells of post-thymic origin. PTCL represent a relatively uncommon group of hematologic malignancies within non-Hodgkin lymphomas (NHL), accounting for about 10% of NHL cases. Among PTCL cases worldwide, the most common subtypes include PTCL-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), NK/T-cell lymphoma, adult T-cell leukemia/lymphoma (ATLL), ALK-positive anaplastic large cell lymphoma (ALCL), and ALK-negative ALCL; subtypes such as enteropathy-associated T-cell lymphoma (EATL) and primary cutaneous ALCL are relatively rare with ALCL more common than NK/T or ATLL in the United States. PTCLs are less responsive to and have less frequent durable remissions with standard chemotherapy regimens such as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and thus carry a poorer prognosis compared to diffuse large B-cell lymphomas. In prospective randomized studies, PTCLs have been included with aggressive B-cell lymphomas. However, due to small sample size, it has not been possible to assess the impact of chemotherapy in this subgroup and there have been no randomized studies comparing the chemotherapy regimens exclusively in persons with PTCL. The poor results with conventional chemotherapy have led many to explore the role of high-dose therapy followed by autologous stem cell rescue (HDT/ASCR) as a first-line consolidation therapy option. In persons with relapsed or refractory PTCL, several options are available. NCCN guidelines advocate second-line chemotherapy prior to transplant in relapsed persons and also support the use of second-line chemotherapy in subjects who are not candidates for transplant. Pralatrexate is a new antifolate with high affinity for reduced folate carrier type 1 (RFC-1), and has shown significant activity in persons with relapsed/refractory T-cell lymphoma and is considered an appropriate second-line therapy option in individuals who are candidates for transplant, as well as though who are not eligible. In September 2009, pralatrexate became the first Food and Drug Administration (FDA)-approved single agent for the treatment of persons with relapsed or refractory PTCL. Results from the pivotal, international, phase II study (PROPEL) showed that pralatrexate resulted in an overall response rate (ORR) of 29% (complete response [CR] 11%; response assessed by an independent review) in pretreated subjects with relapsed or refractory PTCL (n=109 evaluable). Although treatment with pralatrexate resulted in an improvement in ORR, other clinical benefits such as improvement in progression-free survival or overall survival have not been demonstrated.

CTCL also represent a heterogeneous group of NHL characterized by an initial inflammation of the skin with clonally-derived malignant T lymphocytes. The diversity of clinical and pathologic manifestations among subsets of CTCL has led to much controversy over its diagnosis and classification and to the establishments of consensus guidelines by a joint effort of the World Health Organization and European Organization for Research and Treatment of Cancer (WHO-EORTC) in 2005. The two most common types of CTCL are MF, which is generally indolent in behavior, and SS, an aggressive leukemic form of the disease. Together, MF and SS comprise 54% of all CTCL. In 2007, NCCN created its first guideline on MF/SS. There are no sufficient randomized studies to recommend a preferred treatment strategy for MF/SS, nor do universally accepted treatment strategies exist. The chronicity of the disease results in many individuals being treated with multiple therapies in their lifetime, including: skin-directed therapies (e.g., ultraviolent light, topicals, and radiation), systemic agents ranging from retinoids to other biologics to chemotherapy, and an emerging role for allogeneic stem cell transplantation. Pralatrexate has also demonstrated activity in persons with CTCL. In a multicenter dose-finding study, pralatrexate 10 mg/m2 to 30 mg/m2 (administered weekly for 2 of 3 weeks or 3 of 4 weeks) was evaluated in persons with relapsed or refractory CTCL (n=54; MF, n=38 [70%]; SS, n=15 [28%]). Subjects had received a median of 4 prior systemic therapies (range, 1 to 11). The recommended dose identified was 15 mg/m2 weekly for 3 weeks of a 4 week cycle. The ORR for all evaluable subjects was 41% (CR in 5.5%). Thus, low-dose pralatrexate was shown to have high activity in persons with heavily pretreated CTCL. NCCN guidelines support the use of pralatrexate as second-line therapy in the treatment of MF/SS.

POSITION STATEMENT:

Pralatrexate (Folotyn) meets the definition of medical necessity for members meeting ALL of the following criteria:

1. Indication for use is treatment of peripheral T-cell lymphomas (PTCL) or cutaneous T-cell lymphomas (CTCL)

2. Member’s disease is relapsed or refractory

3. Member has tried/failed one or more systemic chemotherapy regimens (e.g., bexarotene [Targretin], gemcitabine [Gemzar])

4. Member is receiving BOTH of the following concomitantly:

a. Vitamin B12 1 mg intramuscularly every 8 to 10 weeks

b. Folic acid 1 to 1.25 mg orally once daily

5. Dose does not exceed 30 mg/m2 IV once weekly

Duration of approval: 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 IT’S USAGE.

FDA-approved

• 30 mg/m2 administered as an intravenous push over 3 to 5 minutes once weekly for 6 weeks in 7-week cycles

• Prior to initiating, supplement with vitamin B12 1 mg intramuscularly every 8-10 weeks and folic acid 1.0-1.25 mg orally on a daily basis

Dose Adjustments

The management of severe or intolerable adverse reactions may require dose omission, reduction, or discontinuation of pralatrexate therapy. For dose modifications and omissions, refer to tables 1-3.

Table 1

Table 1: Dose adjustments for mucositis

Mucositis Grade† on Day of Treatment

Action

Dose upon recovery to less than or equal to Grade 1 mucositis

Grade 2

Omit dose

Continue prior dose

Grade 2 recurrence

Omit dose

20 mg/m2

Grade 3

Omit dose

20 mg/m2

Grade 4

Stop Therapy

 

†Based on National Cancer Institute-Common Terminology Criteria for Adverse Events (refer to definition section)

Table 2

Table 2: Dose adjustments for hematologic toxicities

Blood Count on Day of Treatment

Duration of Toxicity

Action

Dose upon restart

Platelets less than 50,000/mcL

1 week

Omit dose

Continue prior dose

2 weeks

Omit dose

20 mg/m2

3 weeks

Stop therapy

--

ANC 500-1,000/mcL and NO fever

1 week

Omit dose

Continue prior dose

ANC 500-1,000/mcL with Fever

Or

ANC less than 500/mcL

1 week

Omit dose, give

G-CSF or GM-CSF

Continue prior dose with G-CSF or GM-CSF

2 weeks or recurrence

 

20 mg/m2 with G-CSF or GM-CSF

3 weeks or 2nd recurrence

Stop therapy

--

ANC, absolute neutrophil count; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte macrophage stimulating factor

Table 3

Table 3: Dose adjustments for all other treatment-related toxicities

Toxicity Grade† on Day of Treatment

Action

Dose upon recovery to less than or equal to Grade 2

Grade 3

Omit dose

20 mg/m2

Grade 4

Stop therapy

 

†Based on National Cancer Institute-Common Terminology Criteria for Adverse Events (refer to definition section)

Drug Availability

Sterile, single-use vials containing pralatrexate at a concentration of 20 mg/mL in the following presentations:

• 20 mg of pralatrexate in 1 mL solution in a vial (20 mg / 1 mL)

• 40 mg of pralatrexate in 2 mL solution in a vial (40 mg / 2 mL)

PRECAUTIONS:

Boxed Warning

None

Contraindications

None

Precautions/Warnings

• Thombocytopenia, neutropenia, and anemia: monitor blood counts and omit and/or reduce dose for hematologic toxicities.

• Mucositis: treatment with pralatrexate may cause mucositis. If ≥ Grade 2 mucositis is observed, dose should be modified. Monitor at least weekly.

• Dermatologic reactions: reactions, including fatal reactions, have occurred and may be progressive and increase in severity with further treatment. Monitor closely and omit and/or reduce dose or discontinue therapy.

• Tumor lysis syndrome: anticipate, monitor, and treat promptly.

• Hepatic toxicity: monitor for toxicity; refer to dosage/administration section for dose adjustments for toxicities.

• Renal toxicity: members with moderate to severe renal function impairment may be at greater risk for increased exposure and toxicity. Monitor renal function and for systemic toxicity; adjust accordingly. Avoid pralatrexate in those with end stage renal disease including those undergoing dialysis unless the potential benefit outweighs the risk.

• Pregnancy Category D: women should avoid becoming pregnant while being treated with pralatrexate.

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding:

J9307

Injection, pralatrexate, 1 mg

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

C84.00 – C84.09

Mycosis fundoides

C84.10 - C84.19

Sezary’s disease

C84.40 – C84.49

Peripheral T-cell lymphoma, not classified

C84.60 – C84.79

Anaplastic large cell lymphoma, ALK-positive & ALK-negative

C84.93

Mature T/NK-cell lymphomas, unspecified, intra-abdominal lymph nodes

C85.80 – C85.89

Other specified types of non-Hodgkin lymphoma

Z85.79

Personal history of other malignant neoplasms of lymphoid, hematopoietic and related tissues

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) or Local Coverage Determination (LCD) were found at the time of the last guideline revised date.

DEFINITIONS:

Cancer: A term for diseases in which abnormal cells divide without control and can invade nearby tissues.

Common Terminology Criteria for Adverse Events v4.0 (CTCAE)

Grade

Description

1

Mild; asymptomatic or mild symptoms; clinical diagnostic observations only; intervention not indicated

2

Moderate; minimal, local or noninvasive intervention indicated; limited age-appropriate instrumental activities of daily living

3

Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living

4

Life-threatening consequences; urgent intervention indicated

5

Death related to adverse event

Cutaneous T-cell lymphoma: any of a group of T-cell non-Hodgkin lymphoma that begins in the skin as an itchy, red rash that can thicken or form a tumor. The most common types are mycosis fungoides and Sezary syndrome.

Lymphoma: cancer that begins in cells of the immune system. There are two basic types: Hodgkin lymphoma and non-Hodgkin lymphoma.

Mucositis: inflammation of a mucous membrane.

Mycosis fungoides: A type of non-Hodgkin lymphoma that first appears on the skin and can spread to the lymph nodes or other organs such as the spleen, liver, or lungs

Non-Hodgkin Lymphoma: any of a large group of cancers of lymphocytes (white blood cells). The can be formed from either B-cells or T-cells. T-cell non-Hodgkin lymphomas include mycosis fungoides, anaplastic large cell lymphoma, and precursor T-lymphoblastic lymphoma. Lymphomas that occur after bone marrow or stem cell transplantation are usually B-cell non-Hodgkin lymphomas. Prognosis and treatment depend on the stage and type of disease. Also called NHL.

Peripheral T-cell lymphoma: One of a group of aggressive (fast-growing) non-Hodgkin lymphomas that begins in mature T lymphocytes (T cells that have matured in the thymus gland and goes to other lymphatic sites in the body, including lymph nodes, bone marrow, and spleen.). Also called mature T-cell lymphoma.

Refractory: does not respond to treatment. The cancer may be resistant at the beginning of treatment or it may become resistant during treatment. Also called resistant cancer.

Relapse: The return of a disease or the signs and symptoms of a disease after a period of treatment.

Sezary syndrome: A cancer that affects the skin. It is a form of cutaneous T-cell lymphoma.

RELATED GUIDELINES:

Bexarotene (Targretin®) Capsules, 09-J1000-41
Granulocyte Colony Stimulating Factors, 09-J0000-62

Gemcitabine (Gemzar®) IV, 09-J0000-96

Vitamin B-12 Injections, 09-J0000-10

Vorinostat (Zolinza®) Capsules, 09-J1000-54

OTHER:

None applicable.

REFERENCES:

1. AHFS Drug Information. Bethesda (MD): American Society of Health-System Pharmacists, Inc; 2013 [cited 2013 Dec 31]. In: STAT!Ref Online Electronic Medical Library [Internet]. Available from: http://online.statref.com/.

2. Allos Therapeutics. Folotyn (pralatrexate) injection. 2011 [cited 2013 Dec 31]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=5e4cf15b-bf7b-4b83-863e-e9ef27741a51/.

3. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2013 [cited 2013 Dec 31]. Available from: http://www.clinicalpharmacology.com/.

4. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 2013 Dec 31]. Available from: http://clinicaltrials.gov/.

5. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2013 Dec 31]. Available from: http://www.thomsonhc.com/.

6. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Non-Hodgkin’s Lymphomas, v. 1.2014 [cited 2013 Dec 31]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.

7. NCCN Drugs & Biologics Compendium [Internet]. Fort Washington (PA): National Comprehensive Cancer Network; 2013 [cited 2013 Dec 31]. Available from: http://www.nccn.org/professionals/drug_compendium/content/contents.asp/.

8. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2013 [cited 2013 Dec 31]. 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 02/12/14.

GUIDELINE UPDATE INFORMATION:

03/15/10

New Medical Coverage Guideline.

01/01/11

Revision; consisting of updating coding.

02/15/11

Review and revision; consisting of updating coding and references.

03/15/12

Review and revision to guideline; consisting of dosage, coding and references.

03/15/13

Review and revision to guideline; consisting of revising/reformatting position statement to include treatment of cutaneous T-cell lymphomas and to require failure of previous chemotherapy; revised description section, dosage/administration, and precaution section; updated references; added pertinent definitions and related guidelines.

03/15/14

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

11/01/15

Revision: ICD-9 Codes deleted.

Date Printed: September 30, 2016: 04:25 AM