Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Pralatrexate (Folotyn®) for Injection

Policy #:08.00.83g

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract.

MEDICALLY NECESSARY

Pralatrexate (Folotyn®) for injection is considered medically necessary and, therefore, covered for the treatment of individuals with the following types of relapsed or refractory peripheral T-cell lymphoma (PTCL),as outlined below:


ADULT T-CELL LEUKEMIA/LYMPHOMA
  • Second line therapy (with intention to proceed to high-dose therapy/allogeneic stem cell rescue [HDT/ASCR]) or subsequent therapy to HDT/ASCR as a single agent for nonresponders to first-line therapy for acute disease or lymphoma subtypes

MYCOSIS FUNGOIDES (MF)/SEZARY SYNDROME (SS)
  • As first-line therapy in low or standard doses for any of the following:
    • Stage IB-IIA MF with histological evidence of folliculotropic or large cell transformation or Stage IIB with generalized tumor lesions with or without skin-directed therapy
    • Stage IV non-Sezary or visceral disease, with or without radiation therapy for local control
  • As preferred systemic therapy in low doses as treatment for:
    • Stage IB-IIA MF that is refractory to multiple previous therapies or progression
    • Stage IIB MF with limited tumor lesions refractory to multiple previous therapies or progression, with or without skin-directed therapies
    • Stage IIB MF with generalized tumor lesions that is relapsed with T3 disease or has persistent T3 disease with or without skin-directed therapies
    • Stage III MF that is refractory to multiple previous therapies or progression
    • Stage IV Sezary syndrome that is refractory to multiple previous therapies or progression
    • Stage IV non Sezary or visceral disease (solid organ) that is relapsed or persistent with or without radiation therapy for local control
  • As preferred systemic therapy in standard doses as treatment for:
    • Stage IIB MF with limited tumor lesions refractory to multiple previous therapies or progression, with or without skin-directed therapies
    • Stage IIB MF with generalized tumor lesions that is relapsed with T3 disease or has persistent T3 disease with or without skin-directed therapies
    • Stage IV non Sezary or visceral disease (solid organ) that is relapsed or persistent with or without radiation therapy for local control

PRIMARY CUTANEOUS CD30+T-CELL LYMPHOPROLIFERATIVE DISORDERS
  • As a single agent therapy for primary cutaneous anaplastic large cell lymphoma (ALCL) with multifocal lesions or cutaneous ALCL with regional nodes (excludes systemic ALCL) as either of the following:
    • Primary treatment
    • Therapy for relapsed or refractory disease

OTHER PERIPHERAL T-CELL LYMPHOMA
  • As a single agent for second-line or subsequent therapy for relapsed or refractory angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma not otherwise specified, anaplastic large cell lymphoma, enteropathy-associated T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma, nodal peripheral T-cell lymphoma with TFH phenotype, or follicular T-cell lymphoma.

EXPERIMENTAL/INVESTIGATIONAL

All other uses of pralatrexate (Folotyn®) for injection are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.
Guidelines

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, pralatrexate (Folotyn®) for injection is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA)

The FDA granted initial approval for the use of pralatrexate (Folotyn®) to Allos Therapeutics, Inc. (Westminster, CO) on September 24, 2009. As of September of 2012, Allos Therapeutics, Inc. is now a subsidiary of Spectrum Pharmaceuticals Inc.

PEDIATRIC USE

The safety and effectiveness of pralatrexate (Folotyn®) in pediatric individuals have not been established.

Description

Non-Hodgkin's lymphoma (NHL) is a cancer that originates in the lymphocytes, a type of white blood cell that is part of the body's immune system. There are two main types of lymphocytes: B lymphocytes (B-cells) and T lymphocytes (T-cells). T-cell lymphomas comprise less than 15 percent of NHL cases in the United States. Peripheral T-cell lymphoma (PTCL), a T-cell NHL, accounts for about 5 percent of all lymphomas and reflects a biologically diverse and uncommon group of blood cancers.

According to the Revised European American Lymphoma (REAL) World Health Organization (WHO), peripheral T-cell lymphoma is classified into four groups: cutaneous, extranodal, nodal, and leukemic.

Types of Peripheral T-Cell Lymphomas
CutaneousMycosis fungoides
Sezary syndrome
Primary cutaneous CD30+ T-cell lymphoproliferative disorders
ExtranodalNK/T-cell lymphoma, nasal type
Enteropathy- type T-cell lymphoma
Hepatosplenic T-cell lymphoma
Subcutaneous panniculitis-like T-cell lymphoma
Nodal Peripheral T-cell lymphoma, unspecified
Anaplastic large cell lymphoma
Angioimmunoblastic T-cell lymphoma
Leukemic Adult T-cell leukemia/lymphoma
T-cell prolymphocyte leukemia
T-cell large granular lymphocytic leukemia
Aggressive NK cell leukemia
Uncertain lineage and usage Blastic NK cell lymphoma


Pralatrexate (Folotyn®) is a cytotoxic anticancer agent that acts as a folate analogue metabolic inhibitor leading to interruption of DNA synthesis. This interruption in DNA synthesis inhibits cell growth and can lead to cell death. Pralatrexate (Folotyn®) is the first US Food and Drug Administration (FDA)--approved drug for relapsed or refractory PTCL. It received FDA approval in September 2009 under the accelerated approval program. The FDA label states that clinical benefits such as improvement in progression-free survival or overall survival have not been demonstrated.

CLINICAL STUDIES

The FDA summary report notes that the approval is based on a single study called the PROPEL trial, (Pralatrexate in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma), which was conducted under a special protocol assessment agreement. Because of the rarity of the disease and the absence of effective therapies for individuals with relapsed or refractory PTCL, it was agreed that, depending on the magnitude of the response rate, the duration of response, and the risk-benefit ratio, a single study of at least 100 individuals may be sufficient to support FDA approval.

The PROPEL trial was an open-label, single-arm, multicenter, Phase 2 international trial that evaluated 109 individuals with relapsed or refractory PTCL. Individuals were treated with pralatrexate (Folotyn®) at 30 mg/m2 once weekly by IV push, over 3-5 minutes, for 6 weeks in 7-week cycles until disease progression or unacceptable toxicity.

Individuals in the study had histologically confirmed PTCL by independent central review using the Revised European American Lymphoma (REAL) World Health Organization (WHO) disease classification, and relapsed or refractory disease after at least one prior treatment. The median number of prior systemic therapies was 3 (range 1-12). Approximately 24 percent of individuals did not have evidence of response to any previous therapy, and 63 percent of individuals did not have evidence of response to their most recent prior therapy before entering the study.

The primary efficacy endpoint was overall response rate (i.e., complete response, complete response unconfirmed, and partial response). The key secondary efficacy endpoint was duration of response, which was measured from the first day of documented response to disease progression or death. The response rate was 27 percent. Of the responders, 66 percent responded within the first cycle. The median time to first response was 45 days (range 37-349 days). The toxicity profile of pralatrexate (Folotyn®) treatment was found to be acceptable and comparable to methotrexate, a similar drug in the folate analogue metabolic inhibitor class.

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
References


American Cancer Society (ACS). Cancer Reference Information. Detailed Guide: Lymphoma, Non-Hodgkin Type. What Is Non-Hodgkin Lymphoma? [ACS Web site]. 05/31/2016. Available at: http://www.cancer.org/cancer/non-hodgkinlymphoma/detailedguide/non-hodgkin-lymphoma-what-is-non-hodgkin-lymphoma. Accessed November 29, 2017.

American Hospital Formulary Service (AHFS). Pralatrexate. [LexiComp Web site]. 2017. Available at: http://online.lexi.com/lco/action/eula/show# [via subscription only]. Accessed November 29, 2017.

Elsevier Gold's Standard Clinical Pharmacology Compendium. Pralatrexate. [ClinicalKey Web site. 03/30/2017. Available at: https://www.clinicalkey.com/#!/content/drug_monograph/6-s2.0-3684 [via subscription only]. Accessed November 29, 2017.

Folotyn® (pralatrexate). [prescribing information] Westminster, CO: Spectrum Pharmaceuticals, Inc. November 2016. Available at: http://folotyn.com/HCP/downloads/folotyn-pi_Nov2016.pdf. Accessed November 21, 2017.

Horwitz SM, Olsen EA, Duvic M, et al. Review of the treatment of mycosis fungoides and Sezary syndrome: a stage-based approach. JNCCN.2008;6(4):436-442.

Lexi-Drugs Compendium. Pralatrexate. [Lexicomp Online Web site]. 11/15/2017. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed November 29, 2017.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. T-Cell Lymphomas. V1.2018. 11/08/2017. Available at: https://www.nccn.org/professionals/physician_gls/pdf/t-cell.pdf. Accessed November 28, 2017.

National Comprehensive Cancer Network (NCCN). NCCN Drug and Biologics Compendium. Pralatrexate. [National Comprehensive Cancer Network Web site]. 11/15/2017. Subscription required. Available at: https://www.nccn.org/professionals/drug_compendium/content/. Accessed November 21, 2017.

O'Connor OA, Pro B, Pinter-Brown L, et al. Pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma: results from the pivotal PROPEL study. J Clin Oncol.2011;29(9):1182-1189.

Olsen E, Vonderheid E, Pimpinelli N. Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ICSL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood.2007;110(6):1713-1722.

Rodriguez J, Gutierrez A, Maritnez-Delgado B. Current and future aggressive peripheral T-cell lymphoma treatment paradigms, biological features and therapeutic molecular targets. Crit Rev Oncol/Hematol. 2009;71:181-198.

Truven Health Analytics Inc. Micromedex® 2.0 Healthcare Series. DrugDex®. Pralatrexate. [Micromedex Web site]. 10/17/2017. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed November 29, 2017.

US Food and Drug Administration (FDA). Center for Biologics Evaluation and Research. Folotyn®. Approval letter. [FDA Web site]. 09/24/09. Available at:
http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2009/022468s000ltr.pdf. Accessed November 29, 2017.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs@FDA.Drug Details: pralatrexate (Folotyn®) [FDA Web site]. 05/2016. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022468s012lbl.pdf. Accessed November 21, 2017.





Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

SEE ATTACHMENT A


HCPCS Level II Code Number(s)

J9307 Injection, pralatrexate, 1 mg


Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References

Attachment A: Pralatrexate (Folotyn®) for Injection
Description: ICD-10 Codes Eligible to be Reported for Pralatrexate (Folotyn®) for Injection




Policy History

08.00.83g
02/21/2018This policy has undergone a routine review and the medical necessity criteria have been revised to reflect the United States Food and Drug Administration (FDA) labeling and National Comprehensive Cancer Network (NCCN) compendia.


Effective 10/05/2017 this policy has been updated to the new policy template format.

Version Effective Date: 02/21/2018
Version Issued Date: 02/21/2018
Version Reissued Date: N/A

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