Subject:
Pralatrexate (Folotyn)
Description:
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IMPORTANT NOTE:
The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.
Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
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Peripheral T-cell lymphoma consists of a group of rare and aggressive non-Hodgkin lymphomas that develop from T-cells in various stages of maturity. The World Health Organization has classified peripheral T-cell lymphoma into two main categories: precursor T/natural killer cell neoplasms and peripheral T/natural killer cells neoplasms.
Pralatrexate (FolotynTM) is a folate analogue metabolic inhibitor and has an FDA approved indication for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma. Pralatrexate is a novel 10-dezaaminopterin antifolate, structurally similar to methotrexate. Pralatrexate is administered as an intravenous (IV) push. The FDA granted accelerated approval for FolotynTM in September 2009 based on data from the PROPEL study. The PROPEL study is a Phase II single-arm, multicenter, international trial conducted in 109 patients with relapsed or refractory peripheral T-cell lymphoma that showed 27% overall response rate (which included the total response based on complete response, complete response unconfirmed and partial response) to treatment with pralatrexate (FolotynTM). The median time to first response was 45 days. The median duration of response was about 9.4 months. Common adverse events included thrombocytopenia, mucositis, neutropenia, and anemia. Pralatrexate has been associated with severe dermatologic reactions, which may result in death. Tumor lysis syndrome has also been reported in patients with lymphoma receiving pralatrexate.
The label for pralatrexate (Folotyn™) was updated in May 2012 to include additional guidance to physicians regarding the use in patients with end stage renal disease undergoing dialysis. Patients with moderate to severe renal function impairment may be at greater risk for increased exposure and toxicity. Monitor patients for renal function and systemic toxicity and adjust dosing accordingly. Avoid Folotyn™ use in patients with end stage renal disease including those undergoing dialysis unless the potential benefit justifies the potential risk.
[INFORMATIONAL NOTE: Folotyn (pralatrexate injection) has the following warnings and precautions for thrombocytopenia, neutropenia, anemia, mucositis, dermatoligc reactions, tumor lysis syndrome, hepatic toxicity, increased risk of toxicity with renal impairment, and embryo-fetal toxicity. ]
Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)
The requirements of the Horizon BCBSNJ Pralatrexate (Folotyn) Program may require a precertification/prior authorization via MagellanRx Management. These requirements are member-specific: please verify member eligibility and requirements through the Horizon Provider Portal (www.horizonblue.com/provider). Ordering clinicians should request pre-certification from MagellanRx Management at ih.magellanrx.com or call 1-800-424-4508 (when applicable).
1. The prescriber is a specialist in the area of the patient’s diagnosis (e.g. oncologist) or has consulted with a specialist in the area of the patient’s diagnosis.
2. Pralatrexate (FolotynTM) is medically necessary based on the FDA approved indication for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma(PTCL) including angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma not otherwise specified, anaplastic large cell lymphoma, enteropathy-associated T-cell lymphoma, or monomorphic epitheliotropic intestinal T-cell lymphoma.
[INFORMATIONAL NOTE: Per the FDA approved package insert, if a patient is pregnant or becomes pregnant, the use of pralatrexate should be evaluated before continuing use.]
3. The initial and continuation therapy with pralatrexate (FolotynTM), when medically necessary, will be covered every 7 months at the FDA-recommended dose of 30 mg/m2 intravenous push once weekly for 6 weeks in 7-week cycles until disease progression or intolerable toxicity.
· For patients with severe renal impairment (eGFR 15 to <30 mL/min/1.73 m2), the recommended dose is 15 mg/m2
[INFORMATIONAL NOTE: Based on the FDA recommendation for pralatrexate, it is recommended that patients be supplemented with vitamin B12 intramuscularly no more than 10 weeks prior to first dose of FolotynTM and every 8-10 weeks. Folic acid 1-1.25 mg should be administered during the 10-day period preceding first dose of FolotynTM and dosing should continue during the full course of therapy and for 30 days after the last dose of FolotynTM. The use of folic acid and vitamin B12 supplementation during pralatrexate therapy has been shown to reduce its toxicity].
4. Pralatrexate (Folotyn) is considered medically necessary for the following off-label use:
- T-Cell Lymphomas- Adult T-Cell Leukemia/Lymphoma (ATLL): Second-line or subsequent therapy as a single agent for nonresponders to first-line therapy for acute or lymphoma subtypes
- Primary Cutaneous Lymphomas - Mycosis Fungoides (MF)/Sezary Syndrome (SS): Systemic therapy as primary treatment for
· Stage IB MF with a higher disease burden (eg, predominantly plaque disease) and B1 blood involvement, with or without skin-directed therapy
· Stage IIB MF with generalized tumor lesions, with or without skin-directed therapy (preferred)
· 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 (preferred)
· Large cell transformation (LCT) with generalized cutaneous or extracutaneous lesions, with or without skin-directed therapy (preferred)
· Systemic therapy as treatment for
· Relapsed or persistent stage IB-IIA MF 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 therapy (preferred)
· Relapsed or persistent stage IIB MF with generalized tumor lesions, with or without skin-directed therapy (preferred)
· Stage IIB MF with generalized tumor lesions refractory to multiple previous therapies
· Relapsed or persistent stage III MF, with or without skin-directed therapy
· Stage III MF that is refractory to multiple previous therapies
· Relapsed or persistent stage IV Sezary syndromes
· Relapsed or persistent stage IV non Sezary or visceral disease (solid organ), with or without radiation therapy for local control (preferred)
· Large cell transformation (LCT) with limited cutaneous lesions that is refractory to multiple previous therapies (preferred)
· Relapsed or persistent LCT with generalized cutaneous or extracutaneous lesions, with or without skin-directed therapy (preferred)
- Primary Cutaneous Lymphomas - Primary Cutaneous CD30+ T-Cell Lymphoproliferative Disorder: Single-agent therapy for primary cutaneous anaplastic large cell lymphoma (ALCL) with multifocal lesions or cutaneous ALCL with regional nodes (excludes systemic ALCL) as
- Primary treatment; OR
- Therapy for relapsed or refractory disease
- T-cell Lymphomoas- Peripheral T-Cell lymphomas: Second-line or initial palliative intent therapy and subsequent therapy for relapsed/refractory anaplastic large cell lymphoma, peripheral T-cell lymphoma not otherwise specified (preferred), angioimmunoblastic T-cell lymphoma, enteropathy-associated T-cell lymphoma (preferred), monomorphic epitheliotropic intestinal T-cell lymphoma (preferred), nodal peripheral T-cell lymphoma with TFH phenotype (preferred), or follicular T-cell lymphoma (preferred), as a single agent
- T-Cell Lymphomas - Adult T-Cell Leukemia/Lymphoma: Second-line or subsequent therapy as a single agent for nonresponders to first-line therapy for acute or lymphoma subtypes
- T-Cell Lymphomas - Extranodal NK/T-Cell Lymphoma, nasal type: Therapy as a single agent for relapsed/refractory disease following additional therapy with an alternate combination chemotherapy regimen (asparaginase-based) not previously used
- T-Cell Lymphomas - Hepatosplenic Gamma-Delta T-Cell Lymphoma: Preferred second-line and subsequent therapy as a single agent for refractory disease after 2 primary treatment regimens
5. Pralatrexate (FolotynTM) is considered investigational in the, but not limited to, the following conditions:
- Non-small cell lung cancer
- Advanced solid tumors
- Treatment of Non-Hodgkins Lymphoma in combination with gemcitabine
- Metastatic head and neck squamous cell cancer
- Unresectable or metastatic esophageal, stomach, or gastroesophageal junction cancer
- Advanced or metastatic relapsed transitional cell carcinoma of the urinary bladder
- Breast cancer
- Pleural mesothelioma
- Non-small cell lung carcinoma
- Non Hodgkin's lymphoma
- Multiple myeloma
- Adenocarcinoma of the gastroesophageal junction
- Esophageal undifferentiated carcinoma
- Ovarian cancer
- Fallopian tube cancer
- Hodgkins lymphoma
Medicare Coverage
There is no National Coverage Determination (NCD). In the absence of an NCD, coverage decisions are left to the discretion of Local Medicare Carriers. Novitas Solutions, Inc, the Local Medicare Carrier for jurisdiction JL, has not issued a determination for this service. Therefore, Medicare Advantage Products will follow the Horizon Policy.
Medicaid Coverage
For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf
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Horizon BCBSNJ Medical Policy Development Process:
This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.
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Index:
Pralatrexate
Folotyn
Peripheral T-cell lymphoma
References:
1. FolotynTM product information. Allos Therapeutics, Inc. Westminster, CO. September 2019.
2. NCCN Drugs and Biologics Compendium™. Pralatrexate. 2020. [Available at: http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=348][cited February 2020]
3. Gold Standard, Inc. Pralatrexate. Clinical Pharmacology [database online]. Available at: http://www.clinicalpharmacology.com. Accessed: February 4, 2013.
4. Micromedex® Healthcare Series. n.d. Thomson Healthcare, Greenwood Village, CO. 04 Feb. 2013 http://www.thomsonhc.com.
5. AHFS Consumer Medication Information. Bethesda (MD): American Society of Health-System Pharmacists, Inc.; ©2009. Folotyn [ cited 14 Dec 2009]
6. O’Connor O. Getting the Facts Peripheral T-cell Lymphoma. Lymphoma Research Foundation. [ Available at: http://www.lymphoma.org/atf/cf/%7B0363cdd6-51b5-427b-be48-e6af871acec9%7D/PTCL09.PDF ] [ cited 14 Dec 2009]
7. O’Connor OA, Pro B, Pinter-Brown L, et al. PROPEL: Results of the pivotal, multi-center, phase 2 study of pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). Proc Am Soc Clin Oncol. 2009; Abstract 8561.
8. Horwitz SM, Vose JM, Advani R, Sankhala K, et al. A phase 1-2 a open-label study of pralatrexate and gemcitabine in patients with relapsed or refractory lymphoproliferative malignancies (Abstract 570). Blood. 2008; 112(11):1570.
9. O’Connor OA, Hamlin PA, Portlock C, et al. Pralaxtrexate, a novel class of antifol with high affinity for the reduced folate carrier-type 1, produces marked complete and durable remissions in a diversity of chemotherapy refractory cases of T-cell lymphoma. Br J Haematol. 2007; 139:425-8.
10. O’Connor OA, Horwitz S, Hamlin P. A phase ‘2-1-2’ study of two different doses and schedules of pralatrexate, a high affinity substrate for the reduced folate carrier (RFC-1), in patients with relapsed or refractory lymphoma reveals marked activity in T-cell malignancies. J Clin Oncol. 2009.
11. ClinicalTrials.gov. 10-Propargyl-10-Deazaaminopterin in treating patients with Stage IIIB or Stage IV Non-small cell lung cancer. December 2009. [ Available from: http://clinicaltrials.gov/ct2/show/NCT00004238?term=pralatrexate&rank=8] [ cited 17 Dec 2009]
12. ClinicalTrials.gov. 10-Propargyl-10-Deazaminopterin plus probenecid in treating patients with advanced solid tumors. February 2009. [Available from: http://clinicaltrials.gov/ct2/show/NCT00024245?term=pralatrexate&rank=7 ] [ cited 17 Dec 2009]
13. ClinicalTrials.gov. Study of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma. December 2009. [Available from: http://clinicaltrials.gov/show/NCT00554827 ] [ cited 17 Dec 2009]
14. Horwitz SM, Duvic M, Kim Y, Zain JM, et al. Pralatrexate (PDX) is active in cutaneous T-cell lymphoma: preliminary results of a multi-center dose-finding trial (Abstract 1569) Blood. 2008; 112(11):556.
15. ClinicalTrials.gov. Study of pralatrexate and gemcitabine with B12 and folic acid to treat relapsed/refractory lymphoproliferative malignancies. September 2009. [ Available from: http://clinicaltrials.gov/ct2/show/NCT00481871?term=pralatrexate+gemcitabine&rank=1 ] [ cited 4 Jan 2010]
16. Krug LM, Heelan RT, Kris MG, et al. Phase II trial of pralatrexate (10-propargyl-10-deazaaminopterin, PDX) in patients with unresectable malignant pleural mesothelioma. J Thorac Oncol. 2007;2(4):317-320.
17. Kelly K, Azzoli CG, Zatloukal P, et al. Randomized phase 2b study of pralatrexate versus erlotinib in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) after failure of prior platinum-based therapy. J Thorac Oncol. 2012;7(6):1041-1048.
18. National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: T Cell Lymphomas. Version 3.2018. Accessed March 2018.
19. ClinicalTrials.gov. Pralatrexate. [Available from: https://clinicaltrials.gov/ct2/results?cond=&term=folotyn&cntry=&state=&city=&dist= ] [ cited 20 Feb 2020]
Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)
CPT*
HCPCS
* CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.
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Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.
The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy
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