ModifiedmhnPolicy CP.PHAR.313

Pralatrexate (Folotyn) — Clinical Policy

Defines medical necessity, authorization requirements, dosing limits, and approved indications for pralatrexate (Folotyn) for members covered by the payer across Commercial, HIM, and Medicaid lines of business.

Policy Summary

Payermhn

PolicyPralatrexate (Folotyn) — Clinical Policy

Policy CodePolicy CP.PHAR.313

Change TypeMaterial updates (added NCCN off-label indicationsingle-agent requirementgeneric redirection)

Effective DateFeb 1, 2017

Next Review Date

Key ActionSubmit prior authorization with documentation of diagnosis, prior therapies, prescriber specialty, age, and dosing within limits; include evidence for off-label dosing.

SourceLink

POLICY UPDATE CHANGES

Added NCCN off-label use for subcutaneous panniculitis-like T-cell lymphoma and extended initial approval duration for HIM/Medicaid from 6 to 12 months.

For non-cutaneous T-cell lymphomas, added requirement that Folotyn be prescribed as a single agent per NCCN.

30 mg/m2Maximum dose once weekly

6w/7wStandard dosing schedule

Adults ≥18Minimum age

Rel/ref PTCLFDA-approved indication

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20 mg; 40 mgVial sizes

2025References updated

Coverage Criteria for Pralatrexate (Folotyn)

NCCN-Recommended Off-Label Indications

Covered when ALL of the following are met for NCCN-recommended off-label indications:

ALL of the following

ALL of the following
- Primary cutaneous lymphomas (one of the following): - Mycosis fungoides or Sézary syndrome
- Primary cutaneous anaplastic large cell lymphoma (ALCL) with multifocal lesions, or cutaneous ALCL with regional nodes
- Subcutaneous panniculitis-like T-cell lymphoma with one of the following: 1) Hemophagocytic lymphohistiocytosis, systemic disease, or high tumor burden; 2) Inadequate response to first-line therapy (see Appendix B for examples)
- Other T-cell lymphomas (one of the following): - Adult T-cell leukemia/lymphoma (ATLL) after failure of first-line therapy (see Appendix B for examples) - Extranodal NK/T-cell lymphoma (NKTL) following asparaginase-based therapy (see Appendix B for examples) - Hepatosplenic T-cell lymphoma after failure of 2 prior treatment regimens (see Appendix B for examples) - Breast implant (BI)-associated ALCL after failure of first-line therapy (see Appendix B for examples)
Prescribed by or in consultation with an oncologist or hematologist
Age ≥ 18 years
For diagnoses other than Mycosis fungoides or Sézary syndrome, prescribed as a single agent
If request is for Folotyn, member must use pralatrexate, unless contraindicated or clinically significant adverse effects are experienced
Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)
Prescribed regimen must be FDA-approved or recommended by NCCN
Prior authorization may be required for prior line therapies

Approved and Recommended Regimens

Indication	Regimen
Peripheral T‑Cell Lymphoma (PTCL) — FDA‑approved	30 mg/m2 IV once weekly for 6 weeks in 7‑week cycles until progressive disease or unacceptable toxicity (maximum 30 mg/m2 once weekly)

Indication	Off‑Label Dosing Requirements
NCCN‑recommended off‑label T‑cell lymphomas (see policy for list of diagnoses)	Single‑agent pralatrexate dosing must be within the FDA maximum limit for any FDA‑approved indication OR supported by practice guidelines/peer‑reviewed literature for the relevant off‑label use; prescriber must submit supporting evidence. For diagnoses other than MF/SS, pralatrexate should be prescribed as a single agent.

Regimen Name	Details
Pralatrexate regimen (PTCL)	Pralatrexate 30 mg/m2 IV once weekly for 6 weeks in 7‑week cycles until progression or unacceptable toxicity; maximum 30 mg/m2 once weekly.

Product and Billing Codes

Billing Rule

Coding inclusion not guarantee of coverage — Inclusion or exclusion of any codes does not guarantee coverage; providers should reference up-to-date coding guidance prior to claims submission.

Inclusion or exclusion of any codes does not guarantee coverage. Providers should reference current professional coding guidance and payer-specific billing instructions prior to claims submission. Prior authorization and clinical documentation are required as noted below.

Inclusion or exclusion of codes does not guarantee coverage; verify coding before claim submission

Prior Authorization

Provider actions: Prior authorization and documentation requirements, durations, off-label & brand/generic guidance.

Prior authorization is required. Providers must document diagnosis, line(s) of therapy, oncologist/hematologist consultation, rationale for dose (≤30 mg/m2 once weekly for 6 of 7 weeks unless supported by guidelines/literature for off‑label use), and supporting literature for non‑FDA approved indications. For requests under the HIM pharmacy benefit, indicate whether request is for Folotyn 20 mg/1 mL or Folotyn 40 mg/2 mL (refer to HIM.PA.103 for Folotyn 40 mg/2 mL if pharmacy benefit applies). If brand Folotyn is requested over a generic, submit clinical justification and documentation of intolerance or contraindication to generic when applicable. Approval durations: Medicaid/HIM FL and AZ — 12 months; HIM other states — 12 months for Folotyn 20 mg/1 mL (see HIM.PA.103 for 40 mg/2 mL); Commercial — 6 months or to member's renewal date, whichever is longer. Providers must submit supporting evidence for off‑label uses; prior authorization requests should include complete medical records and supporting literature.

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior authorization and required documentation

Prior authorization is required. Submit documentation that supports diagnosis, prior therapies (when applicable), prescriber specialty, patient age, and that dosing is within policy limits or supported by guidelines/literature.

Diagnosis of PTCL or specified NCCN-recommended indication
Documentation of prior therapy failure or reason for initial palliative intent
Prescriber is an oncologist or hematologist (or consultation documented)
Age ≥ 18 years
Dosing at or below 30 mg/m2 weekly x6 weeks per 7-week cycle, or supporting evidence for off-label dosing

Prior Authorization

Prior authorization required; updated approval durations

Prior authorization is required per Health Plan policy. The policy has been updated to include generic pralatrexate and notes changes to initial approval duration for HIM/Medicaid.

Approval duration: Medicaid/HIM Florida and Arizona – 12 months; HIM (other states) – 12 months for Folotyn 20 mg/1 mL; Commercial – 6 months or to member renewal, whichever is longer

Line of Therapy and Indication Context

Second‑line

Second‑line use: Covered as second‑line therapy: use after failure of at least one prior therapy for PTCL (see Appendix B for examples of prior regimens).

Appendix B lists examples of first‑line and subsequent therapies.

Salvage

Salvage therapy: Covered as salvage/initial palliation option per policy: Folotyn may be used as an initial palliative option for PTCL and for salvage indications as specified by NCCN guidance.

Added as an option in 4Q2021 annual review; single‑agent requirement clarified.

Background

Pralatrexate (Folotyn) is a folate analog metabolic inhibitor that received FDA approval under accelerated approval for the treatment of patients with relapsed or refractory peripheral T‑cell lymphoma (PTCL).

Definitions and Key Terms

PTCL and subtypes

DefinitionPTCL = peripheral T‑cell lymphoma (a group of non‑Hodgkin T‑cell lymphomas)

Included subtypes (examples)Anaplastic large cell lymphoma (ALCL); Angioimmunoblastic T‑cell lymphoma; Enteropathy‑associated T‑cell lymphoma; Monomorphic epitheliotropic intestinal T‑cell lymphoma; Nodal PTCL with TFH phenotype; Follicular T‑cell lymphoma

Classification notePTCL classification is periodically updated; list provided for general guidance (see WHO classification for complete listing)

Accelerated approval (FDA)

Accelerated approval basisApproved under accelerated approval based on overall response rate

Continued approval conditionContinued approval may be contingent upon verification and description of clinical benefit in confirmatory trial(s)

Quick Provider Summary

Denial Risk

Off‑label requests: provide sufficient evidence or expect denial

Non‑FDA approved indications not specifically addressed in this policy may be denied unless the provider supplies adequate documentation consistent with off‑label use policies.

See CP.CPA.09 (Commercial), HIM.PA.154 (HIM), CP.PMN.53 (Medicaid) for required supporting evidence

Prior Authorization

Prior auth quick checklist: diagnosis, prior therapies, dose, prescriber specialty

Include key items with the prior authorization submission: diagnosis, prior therapies and responses, dosing rationale, and prescriber specialty to expedite review.

Confirm prescriber is an oncologist or hematologist or include consultation note
Document that dosing is within 30 mg/m2 once weekly x6 weeks per 7‑week cycle or provide supporting literature for any variance

Revision History and Policy Changes

2025-07-14material_updateLatest

4Q 2025 annual review added NCCN off-label use for subcutaneous panniculitis-like T-cell lymphoma, added redirection to generic for brand requests, and extended initial approval duration for HIM/Medicaid from 6 to 12 months.

2025-07-14prior_authorization_and_duration_changeLatest

4Q 2025 annual review revised prior authorization language to include generic pralatrexate and extended initial approval duration for HIM/Medicaid from 6 to 12 months.

Policy Summary

Payermhn

PolicyPralatrexate (Folotyn) — Clinical Policy

Policy CodePolicy CP.PHAR.313

Change TypeMaterial updates (added NCCN off-label indicationsingle-agent requirementgeneric redirection)

Effective DateFeb 1, 2017

Next Review Date

Key ActionSubmit prior authorization with documentation of diagnosis, prior therapies, prescriber specialty, age, and dosing within limits; include evidence for off-label dosing.

SourceLink

On This Page

Prior authorization required
Document diagnosis, oncologist/hematologist involvement, prior therapies, and dosing rationale
For off‑label use, submit supporting peer‑reviewed literature or guidelines
For HIM pharmacy benefit requests, specify Folotyn vial size and refer to HIM.PA.103 for 40 mg/2 mL if applicable
If requesting brand over generic, provide clinical justification (intolerance/contraindication)
Approval durations: Medicaid/HIM FL & AZ: 12 months; HIM (other states) 12 months for Folotyn 20 mg/1 mL; Commercial: 6 months or to renewal date

Policy language now references generic pralatrexate

Step Therapy

Preferred alternatives and common first-line regimens

Policy lists preferred therapeutic alternatives and common first-line regimens for PTCL that may be considered prior therapies when assessing medical necessity.

Examples include: brentuximab vedotin + CHP, CHOEP, CHOP, dose-adjusted EPOCH, DHAP, ESHAP
Single-agent options listed include belinostat, brentuximab vedotin, romidepsin

Step Therapy

Single‑agent prescribing requirement

For non-cutaneous T‑cell lymphomas, pralatrexate (Folotyn) must be prescribed as a single agent in accordance with NCCN guidance.

Requests for combination therapy for non-cutaneous T‑cell lymphomas do not meet the single-agent requirement

Documentation Required

Submit supporting clinical documentation

Providers must submit supporting clinical documentation (e.g., office chart notes, laboratory results, or other clinical information) demonstrating the member meets all approval criteria.

Include evidence of diagnosis, prior therapies and responses, dosing rationale, and consultation notes if applicable

Documentation Required

Brand vs. generic — document necessity for brand

Policy revisions allow redirection of brand requests to generic pralatrexate; when requesting brand product, provide documentation justifying medical necessity. HIM formulary status for 40 mg/2 mL vials has specified exclusions.

Brand requests may be redirected to generic — document why brand is clinically necessary
HIM formulary note: Folotyn 40 mg/2 mL is non-formulary for HIM pharmacy benefit in all states except Florida and Arizona

Denial Risk

Non‑FDA indications may be denied without off‑label evidence

Requests for uses that are not FDA‑approved and not addressed in this policy may be denied unless sufficient evidence is provided per the applicable off‑label use policy.

Refer to CP.CPA.09 (Commercial), HIM.PA.154 (HIM), or CP.PMN.53 (Medicaid) for off‑label documentation requirements

Billing Rule

HIM pharmacy benefit — 40 mg/2 mL non‑formulary (most states)

Folotyn 40 mg/2 mL supplied via the HIM pharmacy benefit is non‑formulary and cannot be approved through these criteria for HIM in all states except Florida and Arizona; use the HIM formulary exception process instead.

If request is via HIM pharmacy benefit for Folotyn 40 mg/2 mL in excluded states, refer to HIM.PA.103 for formulary exception instructions

IndicationIndicated for treatment of patients with relapsed or refractory peripheral T‑cell lymphoma (PTCL)

Injection, pralatrexate (billing)

HCPCS codeJ9307 — Injection, pralatrexate, 1 mg

Coding guidanceCodes referenced are for informational purposes only; inclusion or exclusion does not guarantee coverage

Provider actionReference most up‑to‑date professional coding guidance prior to claims submission