Notification



Notification Issue Date:



Medicare Advantage Policy

Title:Pralatrexate (Folotyn®) for Injection
Policy #:MA08.043d

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


The Company makes decisions on coverage based on the Centers for Medicare and Medicaid Services (CMS) regulations and guidance, benefit plan documents and contracts, and the member’s medical history and condition. If CMS does not have a position addressing a service, the Company makes decisions based on Company Policy Bulletins. 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. Although the Medicare Advantage Policy Bulletin is consistent with Medicare’s regulations and guidance, the Company’s payment methodology may differ from Medicare.

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 Policy Bulletin document describes the status of CMS coverage, medical terminology, and/or benefit plan documents and contracts at the time the document was developed. This Policy Bulletin will be reviewed regularly and be updated as Medicare changes their regulations and guidance, scientific and medical literature becomes available, and/or the benefit plan documents and/or contracts are changed.



Policy

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

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.

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 or subsequent therapy as a single agent for nonresponders to first-line therapy for acute disease or lymphoma subtypes

EXTRANODAL NK/T-CELL LYMPHOMA, NASAL TYPE
  • As a single agent therapy for relapsed/refractory disease following additional therapy with an alternate combination chemotherapy regimen (asparaginase-based) not previously used (NCCN-Preferred)

HEPATOSPLENIC GAMMA-DELTA T-CELL LYMPHOMA
  • As a single agent for (NCCN-Preferred) second-line and subsequent therapy for refractory disease after two primary treatment regimens

MYCOSIS FUNGOIDES (MF)/SEZARY SYNDROME (SS)
  • As first-line therapy for any of the following:
    • Stage IIB MF with generalized tumor lesions, with or without skin-directed therapy (as an National Comprehensive Cancer Network [NCCN]-Preferred therapy)
    • Stage III MF, with or without skin-directed therapy
    • Stage IV Sezary syndrome, with or without skin-directed therapy
    • Stage IV non-Sezary or visceral disease (solid organ), with or without radiation therapy for local control (NCCN-Preferred)
    • Large cell transformation (LCT) with generalized cutaneous or extracutaneous lesions, with or without skin-directed therapy (NCCN-Preferred)
  • As systemic therapy as treatment for:
    • Stage IA MF with B1 blood involvement that is refractory to multiple previous therapies, with or without skin-directed therapy
    • Stage IB-IIA MF that is relapsed or persistent, with a higher disease burden (eg, predominantly plaque disease), with or without skin-directed therapy
    • Stage IIB MF with limited tumor lesions refractory to multiple previous therapies, with or without skin-directed therapies (NCCN-Preferred)
    • Stage IIB MF with generalized tumor lesions with relapsed or disease with or without skin-directed therapies (NCCN-Preferred)
    • Stage IIB MF with generalized tumor lesions refractory to multiple previous therapies
    • Stage 3 MF that is relapsed or persistent, with or without skin-directed therapy
    • Stage III MF that is refractory to multiple previous therapies
    • Stage IV Sezary syndrome that is relapsed or persistent
    • Stage IV non Sezary or visceral disease (solid organ) that is relapsed or persistent with or without radiation therapy for local control (NCCN-Preferred)
    • Large cell transformation (LCT) with limited cutaneous lesions that is refractory to multiple previous therapies (NCCN-Preferred)
    • LCT that is relapsed or persistent, with generalized cutaneous or extracutaneous lesions, with or without skin-directed therapy (NCCN-Preferred)

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 and subsequent therapy for relapsed or refractory angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma not otherwise specified (NCCN-Preferred), anaplastic large cell lymphoma, enteropathy-associated T-cell lymphoma (NCCN-Preferred), monomorphic epitheliotropic intestinal T-cell lymphoma (NCCN-Preferred), nodal peripheral T-cell lymphoma with TFH phenotype (NCCN-Preferred), or follicular T-cell lymphoma (NCCN-Preferred)

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.
Policy Guidelines

There is no Medicare coverage determination addressing this drug; therefore, the Company policy is applicable.

BENEFIT APPLICATION

Subject to the applicable Evidence of Coverage, pralatrexate (Folotyn®) for injection is covered under the medical benefits of the Company’s Medicare Advantage products when the medical necessity criteria listed in this medical policy are met.

For Medicare Advantage members, certain drugs are available through either the member's medical benefit (Part B benefit) or pharmacy benefit (Part D benefit), depending on how the drug is prescribed, dispensed, or administered. This medical policy only addresses instances when pralatrexate (Folotyn®) is covered under a member's medical benefit (Part B benefit). It does not address instances when pralatrexate (Folotyn®) is covered under a member’s pharmacy benefit (Part D benefit).

US FOOD AND DRUG ADMINISTRATION (FDA)

The FDA granted initial approval for the use of pralatrexate (Folotyn®) on September 24, 2009 for the treatment of individuals with relapsed or refractory peripheral T-cell lymphoma (PTCL).

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 20 percent of T-cell 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 gamma-delta 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.

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]. 08/01/2018. Available at: http://www.cancer.org/cancer/non-hodgkinlymphoma/detailedguide/non-hodgkin-lymphoma-what-is-non-hodgkin-lymphoma. Accessed March 27, 2019.

American Hospital Formulary Service (AHFS). Pralatrexate. [LexiComp Web site]. 12/01/2010. Available at: http://online.lexi.com/lco/action/eula/show# [via subscription only]. Accessed March 27, 2019.

Elsevier's 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 March 27, 2019.

Folotyn® (pralatrexate). [prescribing information] Westminster, CO: Spectrum Pharmaceuticals, Inc. November 2016. Available at: http://folotyn.com/HCP/Default.aspx. Accessed March 27, 2019.

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.

Leukemia and Lymphoma Society. Peripheral T-Cell Lymphoma Facts. July 2014. Available at: https://www.lls.org/sites/default/files/file_assets/peripheraltcelllymphomafacts.pdf . Accessed March 28, 2019.

Lexi-Drugs Compendium. Pralatrexate. [Lexicomp Online Web site]. 01/24/2019. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed March 27, 2019.

Lymphoma research foundation. T-Cell Lymphoma. 2019. Available at: https://www.lymphoma.org/aboutlymphoma/nhl/tcell/ . Accessed March 27, 2019.

National Institutes of Health. National Caner Institute. The Revised European American Lymphoma Classification (REAL). Available at: https://training.seer.cancer.gov/lymphoma/abstract-code-stage/morphology/real.html . Accessed March 27, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Primary Cutaneous Lymphomas. V2.2019. 12/17/2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/primary_cutaneous.pdf . Accessed March 27, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. T-Cell Lymphomas. V2.2019. 12/17/2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/t-cell.pdf. Accessed March 27, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Drug and Biologics Compendium. Pralatrexate. [National Comprehensive Cancer Network Web site]. Subscription required. Available at: https://www.nccn.org/professionals/drug_compendium/content/. Accessed March 27, 2019.

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]. 02/28/2019. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed March 27, 2019.

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: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed March 27, 2019.


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

MA08.043d
06/17/2019This 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.

MA08.043c
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.

MA08.043b
10/19/2016This policy has been updated to be consistent with the US Food and Drug Administration (FDA) labeling and Compendia. The policy criteria for mycosis fungoides/sezary syndrome was updated based on NCCN.

The following codes were added to the policy: C84.90 C84.91 C84.92 C84.93 C84.94 C84.95 C84.96 C84.97 C84.98 C84.99 C84.A0 C84.A1 C84.A2 C84.A3 C84.A4 C84.A5 C84.A6 C84.A7 C84.A8 C84.A9 C84.Z0 C84.Z1 C84.Z C84.Z3 C84.Z4 C84.Z5 C84.Z6 C84.Z7 C84.Z8 C84.Z9 C91.51 C91.61 C91.90 C91.91 C91.92 C91.Z1 C94.81.

MA08.043a
11/04/2015The Policy section was modified to communicate coverage for relapsed or refractory PTCL based on FDA labeling. The policy also communicates additional coverage for PTCL types based on inclusion in the National Comprehensive Cancer Network (NCCN) compendia.

The following ICD-10 CM codes have been deleted from this policy: C83.50----C83.59; C84.90--C84.99; C84.A0--C84.A9; C84.Z0--C84.Z9; C91.51, C91.90, and C91.92.

The following ICD-10 CM codes have been added to this policy: C91.Z0, C91.Z2, C94.80, and C94.82.

MA08.043
01/01/2015This is a new policy




Version Effective Date: 06/17/2019
Version Issued Date: 06/17/2019
Version Reissued Date: N/A