Last Review Date: 01/05/2023

Date of Origin:  07/29/2014

Dates Reviewed:  07/2014, 07/2015, 07/2016, 01/2017, 01/2018, 01/2019, 01/2020, 01/2021, 01/2022, 01/2023

1. Length of Authorization

Coverage will be provided for 6 months and may be renewed.

2. Dosing Limits

1. Quantity Limit (max daily dose) [NDC unit]:

• Folotyn 20 mg/mL solution for injection, single-dose vial: 24 vials every 49 days
• Folotyn 40 mg/2 mL solution for injection, single-dose vial: 12 vials every 49 days

2. Max Units (per dose and over time) [HCPCS Unit]:

All indications

• 80 billable units weekly x 6 doses in a 7-week cycle

3. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

• Patient is at least 18 years of age; AND

Adult T-Cell Leukemia/Lymphoma ‡ ²

• Used as subsequent therapy as a single agent in patients who did not respond to first-line therapy for acute or lymphoma subtypes

Mycosis Fungoides/Sezary Syndrome ‡ ²

• Patient does NOT have stage IA or IB-IIA mycosis fungoides

Hepatosplenic Gamma-Delta T-Cell Lymphoma ‡ ²

• Used as a single agent as subsequent therapy; AND
• Used for disease that is refractory to two previous first-line therapy regimens

Breast Implant-Associated Anaplastic Large Cell Lymphoma (ALCL) ‡ ²

• Used as subsequent therapy; AND

• Used as single agent therapy for relapsed or refractory disease

Extranodal NK/T-Cell Lymphoma ‡ ²

• Used as single agent therapy for relapsed or refractory disease; AND
• Used as subsequent treatment following additional therapy with an alternate asparaginase-based combination chemotherapy regimen that was not previously used

Peripheral T-Cell Lymphoma (PTCL) † Ф ^1,2

• Used as a single agent for relapsed or refractory disease; AND
• Patient has one of the following PTCL sub-types:
  • Anaplastic large cell lymphoma
  • Peripheral T-cell lymphoma not otherwise specified
  • Angioimmunoblastic T-cell lymphoma
  • Enteropathy-associated T-cell lymphoma
  • Monomorphic epitheliotropic intestinal T-Cell lymphoma
  • Nodal peripheral T-Cell lymphoma with TFH phenotype
  • Follicular T-Cell lymphoma

Primary Cutaneous CD30+ T-Cell Lymphoproliferative Disorders ‡ ²

• Used as a single agent as primary treatment or for relapsed or refractory disease; AND
  • • Patient has primary cutaneous anaplastic large cell lymphoma (ALCL) with multifocal lesions; OR
    • Patient has cutaneous ALCL with regional node (N1) (NOTE: excludes systemic ALCL)

† FDA Approved Indication(s); ‡ Compendia recommended indication(s); Ф Orphan Drug

4. Renewal Criteria ¹

Coverage can be renewed based upon the following criteria:

• Patient continues to meet indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in section III; AND
• Disease response with treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: myelosuppression suppression (e.g., neutropenia, anemia, and/or thrombocytopenia), mucositis, severe dermatologic reactions, tumor lysis syndrome (TLS), increased risk of toxicity (e.g., toxic epidermal necrolysis, mucositis, etc.) in patients with severe renal impairment, hepatic toxicity, etc.

5. Dosage/Administration ^1,4-7

   Indication	Dose
   Peripheral T-Cell Lymphoma (PTCL)	Administer 30 mg/m² intravenously once weekly x 6 doses in 7 week cycles until progressive disease or unacceptable toxicity.
   All Other Indications	Administer 15 mg/m² intravenously once weekly x 3 doses in 4 week cycles until progressive disease or unacceptable toxicity.  -OR- Administer 30 mg/m² intravenously once weekly x 6 doses in 7 week cycles until progressive disease or unacceptable toxicity.

6. Billing Code/Availability Information

       HCPCS Code:

• J9307: injection, pralatrexate, 1 mg; 1 billable unit = 1 mg

NDC:

• Folotyn 20 mg/mL solution for injection, single-dose vial: 72893-0003-xx
• Folotyn 40 mg/2 mL solution for injection, single-dose vial: 72893-0005-xx

7. References

1. Folotyn [package insert]. East Windsor, NJ; Acrotech Biopharma LLC, September 2020. Accessed December 2022.
2. Referenced with permission from the NCCN Drugs and Biologics Compendium (NCCN Compendium^®) pralatrexate. National Comprehensive Cancer Network, 2022. The NCCN Compendium^® is a derivative work of the NCCN Guidelines^®. NATIONAL COMPREHENSIVE CANCER NETWORK^®, NCCN^®, and NCCN GUIDELINES^® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed December 2022.
3. 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 Mar 20;29(9):1182-9. doi: 10.1200/JCO.2010.29.9024. Epub 2011 Jan 18.
4. Foss F, Horwitz SM, Coiffier B, et al. Pralatrexate is an effective treatment for relapsed or refractory transformed mycosis fungoides: a subgroup efficacy analysis from the PROPEL study. Clin Lymphoma Myeloma Leuk. 2012 Aug;12(4):238-43. doi: 10.1016/j.clml.2012.01.010. Epub 2012 Apr 26.
5. Horwitz SM, Kim YH, Foss F, et al. Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood. 2012 May 3;119(18):4115-22. doi: 10.1182/blood-2011-11-390211. Epub 2012 Mar 6.
6. Lunning MA, Gonsky J, Ruan J, et al. Pralatrexate in Relapsed/Refractory HTLV-1 Associated Adult T-Cell Lymphoma/Leukemia: A New York City Multi-Institutional Experience. Blood 120(21):2735-2735. November 2012. 
7. Talpur R, Thompson A, Gangar P et al. Pralatrexate alone or in combination with bexarotene: long-term tolerability in relapsed/refractory mycosis fungoides. Clin Lymphoma Myeloma Leuk. 2014 Aug;14(4):297-304. doi: 10.1016/j.clml.2014.01.010. Epub 2014 Feb 4.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determination (NCD), Local Coverage Article (LCAs) and Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. They can be found at: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications may be covered at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/Article): N/A