ModifiedCentenePolicy N/A

Epcoritamab-bysp (Epkinly) coverage for B‑cell lymphomas

Defines medical necessity and prior authorization criteria for epcoritamab-bysp (Epkinly) for commercial, HIM, and Medicaid lines of business within Centene-affiliated health plans; applies to providers prescribing for adult patients with specified relapsed/refractory B‑cell lymphomas.

Policy Summary

PayerCentene

PolicyEpcoritamab-bysp (Epkinly) coverage for B‑cell lymphomas

Policy CodePolicy N/A

Change TypeMaterial updates to indications and regimen guidance

Effective DateSep 1, 2023

Next Review DateN/A

Key ActionSubmit prior authorization with indication, dosing regimen, and supporting clinical documentation demonstrating prior lines of therapy and dosing per policy.

SourceLink

POLICY UPDATE CHANGES

Added NCCN Compendium supported label use for classic follicular lymphoma.

Updated FDA approved indications to include follicular lymphoma per updated prescribing information.

Per 3Q 2025 annual review, added use in second-line and subsequent therapy in combination with gemcitabine and oxaliplatin.

Appendix D added to specify DLBCL subtypes per NCCN.

Removed specific criteria requirements for histologic transformation of indolent lymphoma to DLBCL.

2FDA‑approved indications (DLBCL and FL)

48 mgmax single dose

6 mo

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Coverage Criteria for Epcoritamab-bysp (Epkinly)

Initial Therapy (B‑Cell Lymphomas)

Covered when ALL of the following are met for B‑cell lymphomas:

Initial Approval - B‑Cell Lymphomas: 1. Diagnosis of one of the following B‑cell lymphoma categories: DLBCL (see Appendix D for subtypes); histologic transformation of follicular or marginal zone lymphoma to DLBCL; post‑transplant lymphoproliferative disorders; HIV‑related B‑cell lymphomas. 2. Prescribed by or in consultation with an oncologist or hematologist. 3. Age >= 18 years. 4. Relapsed or refractory disease. 5. Prior lines of therapy consistent with indication: for DLBCL, member has received >=1 line of systemic therapy (see Appendix B); for FL, member has received >=2 lines of systemic therapy per FDA‑approved labeling or NCCN guidance. 6. Treatment regimen and dosing consistent with policy (e.g., step‑up dosing in Cycle 1 and maintenance dosing schedule) and, when applicable, use in combination (e.g., GemOx) per referenced guidance.

See Appendix B for prior therapy definitions and Appendix D for DLBCL subtypes.

Continuation Therapy

Covered when ALL of the following are met for continuation:

Continued Therapy: 1. Member is currently receiving Epkinly via the Centene benefit, or documentation supports the member has received Epkinly for at least 30 days for a covered indication. 2. Member is responding positively to therapy (clinical benefit as documented by treating provider). 3. The new or continuing dose does not exceed 48 mg per dose (one 48 mg vial) unless the dose increase is supported by practice guidelines or peer‑reviewed literature and prescriber provides supporting evidence. 4. Continued use is consistent with the prescribed regimen schedule (step‑up doses completed and maintenance dosing per policy).

Approval durations: Medicaid/HIM continuation: 12 months; Commercial: 6 months or to the member's renewal date, whichever is longer.

Initial and ongoing therapy coverage criteria

Covered when ALL of the following are met for the specified lymphoma indication and dosing regimen

Indication: Diagnosis consistent with FDA‑approved indications or NCCN Compendium guidance for epcoritamab‑bysp (e.g., relapsed/refractory DLBCL including listed subtypes; relapsed/refractory follicular lymphoma after >=2 lines of systemic therapy).

Appendix D lists DLBCL subtypes per NCCN.

Dosing regimen: Treatment is planned using the approved step‑up subcutaneous dosing schedule (Cycle 1 step‑up doses followed by 48 mg maintenance) and administration schedule per policy (28‑day cycles) until disease progression or unacceptable toxicity. Specific step‑up pattern: DLBCL — 0.16 mg (Day 1), 0.8 mg (Day 8), 48 mg (Day 15) with subsequent 48 mg doses per cycle; FL — 0.16 mg, 0.8 mg, 3 mg, then 48 mg per schedule as detailed in dosing guidance.

See Dosage and Administration section for cycle‑by‑cycle schedule and maximum per dose of 48 mg.

Safety considerations: Provider will monitor for and manage cytokine release syndrome (CRS) and immune effector cell‑associated neurotoxicity syndrome (ICANS) per boxed warning guidance and institutional protocols.

Requests for uses that are not FDA‑approved and are not addressed in this policy are excluded from coverage unless the provider supplies sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policies (commercial: CP.CPA.09; health insurance marketplace: HIM.PA.154; Medicaid: CP.PMN.53).

There are no reported contraindications in the policy document; however, the product includes boxed warnings for cytokine release syndrome (CRS) and immune effector cell‑associated neurotoxicity syndrome (ICANS), which must be considered and managed per the prescribing information.

Use of epcoritamab‑bysp for indications not listed in this policy and without sufficient off‑label evidence per the referenced off‑label policies will be considered not medically necessary.

Operationally, this segment of the document does not list additional specific conditions that are designated as not medically necessary beyond the general off‑label exclusions already stated.

Covered Regimens and Dosing

Indication	Regimen (agent, route)	Cycle 1 step-up / maintenance dosing	Coverage status	Notes / Prior auth documentation
Diffuse large B-cell lymphoma (DLBCL) — relapsed or refractory
Epcoritamab-bysp (Epkinly), subcutaneous
Cycle 1 step-up then maintenance per DLBCL schedule: Day 1 0.16 mg SC; Day 8 0.8 mg SC; Day 15 first full 48 mg SC; Day 22 48 mg SC. Cycles 2–3: Days 1,8,15,22: 48 mg SC. Cycles 4–9: Days 1 and 15: 48 mg SC. Cycle 10+: Day 1: 48 mg SC.
covered
Prior authorization required; submit indication, dosing schedule (including step-up doses and vial strengths), prior lines of therapy and prescriber specialty per policy.

Regimen name	Cycle 1 step-up doses (days)	First full dose and maintenance	Coverage status
DLBCL — Epcoritamab-bysp monotherapy
Day 1: 0.16 mg SC; Day 8: 0.8 mg SC
Day 15: 48 mg SC (first full dose); Day 22: 48 mg SC; subsequent cycles per schedule with 48 mg maintenance as specified in policy
covered

Regimen name	Cycle 1 step-up doses (days)	First full dose and maintenance	Coverage status
Follicular lymphoma (FL) — Epcoritamab-bysp monotherapy
Day 1: 0.16 mg SC; Day 8: 0.8 mg SC; Day 15: 3 mg SC
Day 22: 48 mg SC (first full dose); Cycles 2–3: Days 1,8,15,22: 48 mg SC; Cycles 4–9: Days 1 and 15: 48 mg SC; Cycle 10+: Day 1: 48 mg SC
covered

Indication / line of therapy	Combination regimen	Documentation required	Coverage status / note
DLBCL — second-line and subsequent therapy (per NCCN update)
Epcoritamab-bysp (SC) in combination with GemOx (gemcitabine + oxaliplatin) ± rituximab as referenced by NCCN; dosing of GemOx per NCCN/appendix regimens
Document prior therapies and line of therapy, indication, administered epcoritamab step-up and maintenance dosing, vial strengths used, and supporting clinical notes per prior authorization requirements
covered

Coding and Dosing Limits

Covered CPT/HCPCS Codesmixed

N/A	No explicit billing codes listed in this portion of the policy

HCPCS Codes referencedHCPCS

J9321

Injection, epcoritamab-bysp, 0.16 mg

Maximum per dose

Maximum single dose48 mg per dose (one 48 mg vial)

Policy limit for dose increasesAny dose >48 mg requires supporting practice guidelines or peer-reviewed literature; prescriber must submit evidence

Continuation therapy capNew dose for continuation must not exceed 48 mg per dose

Dose schedule

Cycle 1 step-up schedule (DLBCL)Day 1: 0.16 mg SC; Day 8: 0.8 mg SC; Day 15: first full dose 48 mg SC; Day 22: 48 mg SC

Cycle 1 step-up schedule (FL)Day 1: 0.16 mg SC; Day 8: 0.8 mg SC; Day 15: 3 mg SC; Day 22: first full dose 48 mg SC

Provider Requirements and Authorization

Prior Authorization

Prior Authorization Required

Prior authorization required. Requests must include documentation that member meets the initial approval criteria and the prescriber is an oncologist or hematologist (or consult). Provider must demonstrate medical necessity consistent with the policy.

Prior authorization is required before initiation of therapy.
Prescriber: Oncologist or hematologist (or documented consultation).

Documentation Required

Required Clinical Documentation

Providers must document the clinical indication, full dosing schedule (including step-up dosing and cycle days), actual administered doses and dates, and prior therapies/lines of therapy. For combination regimens (for example GemOx + rituximab per NCCN) include the regimen details and line of therapy. Chart notes, relevant lab results, pathology reports, and prior treatment summaries should be submitted to support the request.

Document indication (e.g., DLBCL subtype, FL, post‑transplant lymphoproliferative disorder).

Line-of-Therapy Considerations

second-line

Second‑line use: Epcoritamab‑bysp (Epkinly) may be used in the second‑line setting where policy line‑of‑therapy rules are met (e.g., DLBCL relapsed/refractory after >=1 prior systemic therapy or FL after >=2 prior systemic therapies) and when prior therapies and line‑of‑therapy are documented; use in combination with gemcitabine + oxaliplatin for second‑line and subsequent therapy is included per NCCN Compendium update.

Documentation of prior therapies and line of therapy required; policy updated per 3Q 2025 to add combination GemOx option.

second-line

Second‑line considerations: Requests for second‑line use must document prior lines of systemic therapy and meet indication‑specific prior therapy rules; dosing must follow the approved step‑up and maintenance schedule or be supported by guidelines if modified. Combination therapy (e.g., with GemOx) is permissible per NCCN guidance added in the 3Q 2025 review.

Providers must submit clinical documentation supporting prior therapies, regimen details, and rationale for combination use when applicable.

Background and Safety Information

Epcoritamab‑bysp (Epkinly) is an FDA‑approved, subcutaneous bispecific antibody authorized under accelerated approval for certain adult patients with relapsed or refractory B‑cell lymphomas, including diffuse large B‑cell lymphoma (DLBCL) and follicular lymphoma (FL) per updated prescribing information. The policy aligns coverage with the labeled indications and NCCN Compendium guidance, specifies a step‑up dosing schedule culminating in a 48 mg maintenance dose, and notes boxed warnings for CRS and ICANS. Non‑FDA indications not covered by this policy require documentation per off‑label use policies for consideration.

DLBCL definition / key term

TermDiffuse large B-cell lymphoma (DLBCL)

Definition noteIncludes DLBCL, NOS and multiple subtypes as listed in Appendix D (e.g., DLBCL arising from follicular lymphoma or marginal zone lymphoma, primary CNS DLBCL, primary mediastinal LBCL, high-grade B-cell lymphomas with MYC/BCL2 rearrangements, Richter transformation, etc.)

ContextDLBCL is an FDA‑approved indication for epcoritamab-bysp per the policy and is enumerated in Appendix D for coverage criteria