CurrentEmblemHealthPolicy N/A

Epkinly (epcoritamab-bysp) coverage for B-cell lymphomas

Defines accepted indications, clinical criteria, exclusions, and coding for Epkinly (epcoritamab-bysp) use in adults with certain relapsed or refractory B-cell lymphomas for EmblemHealth members; applies to providers submitting medication requests processed by Evolent.

Policy Summary

PayerEmblemHealth

PolicyEpkinly (epcoritamab-bysp) coverage for B-cell lymphomas

Policy CodePolicy N/A

Change TypeAdded indication (follicular lymphoma) + template conversion

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization and document failure of at least two systemic therapies before initiating Epkinly as monotherapy.

SourceLink

POLICY UPDATE CHANGES

Added follicular lymphoma indication section based on new FDA label expansion (June 2024).

Converted to new Evolent guideline template and replaced prior guideline UM ONC_1479.

2required prior systemic therapy failures for DLBCL

2required prior systemic therapy failures for follicular lymphoma

J9321HCPCS code

CRS/ICANSboxed warnings

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Coverage Criteria for Epkinly (epcoritamab-bysp)

Initial FDA‑labeled Indications

Covered when ALL of the following are met for the specified diagnosis:

Population: Adult member with one of the specified B-cell lymphomas: relapsed or refractory diffuse large B-cell lymphoma (DLBCL) — including DLBCL arising from indolent lymphoma and high-grade B‑cell lymphoma — OR relapsed or refractory follicular lymphoma.

Prior therapies: Member has failed at least two systemic therapies (for DLBCL this includes prior anti-CD20 monoclonal antibody therapy).>=2 prior systemic therapies

Treatment regimen: Epcoritamab-bysp (Epkinly) to be used as monotherapy per FDA prescribing information.

Concurrent use with other anticancer therapies is exclusionary.

Evidence support: Use is supported by FDA product labeling, CMS-recognized compendia, NCCN/ASCO guidelines, or acceptable peer-reviewed literature per CMS standards.

Safety measures: Initiate treatment using the epcoritamab step-up dosing schedule and monitor for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS); withhold or discontinue per severity as described in the prescribing information.

Coverage will be denied when any of the following exclusionary conditions apply: disease progression while the member is taking Epkinly (epcoritamab-bysp); concurrent use with other anticancer therapies; or dosing that exceeds the single‑dose limit of 48 mg. Requests that do not meet these conditions should be referred for prior authorization per the FDA‑labeled indications and program requirements.

Use of Epkinly for off‑label or investigational indications is considered not medically necessary unless supported by adequate evidence. Acceptable support includes appearance in CMS‑recognized compendia or publication in acceptable peer‑reviewed literature that adequately represents the clinical characteristics and regimen under study, reports clinically meaningful outcomes (for example meeting commonly accepted ASCO thresholds such as a Hazard Ratio < 0.80 or ≥3 months survival benefit for OS/PFS when applicable), and is based on an appropriate experimental design. Case reports, abstracts without full peer‑reviewed articles, or evidence that does not sufficiently represent the patient population or regimen are not adequate support.

Covered Regimens and Administration

Regimen	Indication / Line of therapy	Dosing notes / limits	Coverage status
Epcoritamab-bysp (Epkinly) monotherapy, administered per FDA prescribing information with step‑up dosing schedule	Relapsed or refractory diffuse large B‑cell lymphoma (DLBCL), including DLBCL arising from indolent lymphoma and high‑grade B‑cell lymphoma; member has failed at least two systemic therapies including an anti‑CD20 monoclonal antibody — third‑line or later	Initiate using the epcoritamab step‑up dosage schedule to reduce incidence/severity of cytokine release syndrome (CRS); monitor for CRS and immune effector cell‑associated neurotoxicity syndrome (ICANS). Single‑dose limit: do not exceed 48 mg per dose
Epcoritamab-bysp (Epkinly) monotherapy, administered per FDA prescribing information with step‑up dosing schedule	Relapsed or refractory follicular lymphoma in adults who have failed at least two systemic therapies — third‑line or later	Initiate using the epcoritamab step‑up dosage schedule to reduce incidence/severity of CRS; monitor for CRS and ICANS. Single‑dose limit: do not exceed 48 mg per dose

Coding and Dose Limits

Covered HCPCS CodesHCPCSCovered

J9321

Injection, epcoritamab-bysp, 0.16 mg

Single dose limit

Single-dose maximum48 mg per single dose of Epkinly (epcoritamab-bysp)

Exclusion for exceeding limitRequests will be excluded/denied if dosing exceeds the 48 mg single-dose limit.

Coding relevanceApply the single-dose limit when calculating administered dose units billed under HCPCS code J9321 (epcoritamab-bysp, 0.16 mg).

Provider responsibilityEnsure prescribed and administered single doses do not exceed 48 mg to meet coverage criteria.

Provider Actions, Prior Authorization, and Monitoring

Prior Authorization

Prior Authorization Required

Prior authorization is required for Epkinly (epcoritamab-bysp) when used for FDA‑listed lymphoma indications. Evolent (on behalf of the payer) must authorize medication requests; medications not authorized may be denied and not reimbursable.

Prior authorization required for all requests for Epkinly for lymphoma indications (e.g., relapsed/refractory DLBCL, relapsed/refractory follicular lymphoma).
Evolent processes authorization requests and determines approvability based on documentation and supportive evidence.

Step Therapy

Step-up Dosing and Monitoring for CRS/ICANS

Initiate Epkinly using the manufacturer-recommended step-up dosing schedule to reduce incidence and severity of cytokine release syndrome (CRS). Monitor patients closely for CRS and immune effector cell–associated neurotoxicity syndrome (ICANS). Withhold or permanently discontinue therapy based on severity according to labeling.

Start with the approved step-up dose schedule per prescribing information.

Applicable Lines of Therapy and Salvage Use

salvage

Line of therapy: Epcoritamab is indicated for use after failure of at least two prior systemic therapies (i.e., third-line or later) — defined as salvage-line therapy in the relapsed/refractory setting.>=2 prior systemic therapies

Definitions and Diagnostic Criteria

Relapsed or refractory DLBCL — definition and prior therapy

DefinitionRelapsed or refractory diffuse large B‑cell lymphoma (DLBCL), including DLBCL arising from indolent lymphoma and high‑grade B‑cell lymphoma in adults.

Prior therapy requirementMember must have failed at least two systemic therapies.

Anti‑CD20 requirementFor DLBCL, prior therapy must include an anti‑CD20 monoclonal antibody (e.g., part of regimens such as R‑CHOP, R‑ICE).

Treatment settingEpkinly (epcoritamab-bysp) authorized as monotherapy in the relapsed/refractory (third‑line or later) setting per policy criteria.

Exclusionary situationsRequests are excluded for disease progression while taking Epkinly or concurrent use with other anticancer therapies.

Relapsed or refractory follicular lymphoma — definition and prior therapy

Background

Epkinly (epcoritamab‑bysp) is a bispecific antibody indicated as monotherapy for certain relapsed or refractory B‑cell non‑Hodgkin lymphomas. Treatment carries risks of cytokine release syndrome (CRS) and immune effector cell‑associated neurotoxicity syndrome (ICANS)

Revision History

2025-07template_conversionLatest

Converted to new Evolent guideline template; replaced prior guideline UM ONC_1479 and updated references.

2024-07indication_added

Added follicular lymphoma indication section based on FDA label expansion (June 2024) and updated references and verbiage.