Epkinly - OpenPayer

Coverage Summary

Coverage stance: covered_with_criteria. Scope: defines clinical indications, contraindications/warnings, exclusion criteria, coding, applicable lines of business, and utilization management expectations for Epkinly (epcoritamab-bysp) including FDA-approved and specified off-label uses. Applicable lines of business: Commercial, Exchange/Marketplace, Medicaid. Covered indications summary: Epkinly is authorized for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (including DLBCL arising from indolent lymphoma and high-grade B‑cell lymphoma) after failure of at least two systemic therapies including an anti-CD20 monoclonal antibody; Epkinly in combination with gemcitabine and oxaliplatin is covered for relapsed/refractory DLBCL after failure of two lines when the member is not a candidate for CAR T-cell therapy or transplant; for follicular lymphoma, Epkinly is covered in combination with lenalidomide and rituximab after at least one prior systemic therapy, or as monotherapy after failure of at least two systemic therapies. Dosing threshold: single-dose limit of 48 mg (exceeds which is exclusionary).

Surface thresholds and quick facts

Single dose limit48 mg

DLBCL monotherapy prior therapy requirementFailed at least two systemic therapies including an anti-CD20 monoclonal antibody

DLBCL combination prior therapy requirementFailure of two lines of systemic therapy

Follicular lymphoma combination prior therapy requirementAt least one prior line of systemic therapy

Follicular lymphoma monotherapy prior therapy requirementFailed at least two systemic therapies

Lines of businessCommercial; Exchange/Marketplace; Medicaid

Policy statusMODIFIED (policy history updated December 2025)

Initial Therapy Criteria

Diffuse Large B-Cell Lymphoma (DLBCL) - Covered Indications

Epkinly may be authorized when ALL of the following are met:

ALL of the following

Member is an adult.
Diagnosis of relapsed or refractory diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma.
Member has failed at least two systemic therapies, including an anti-CD20 monoclonal antibody.

DLBCL - Combination Gemcitabine + Oxaliplatin

Epkinly in combination may be authorized when ALL of the following are met:

ALL of the following

Continuation Therapy Criteria

Continuation (re-authorization) criteria exemption

Continuation requests for a not-approvable medication shall be exempt when ALL of the following are met:

ALL of the following

The member has not experienced disease progression on the requested medication.
The requested medication was used within the last year without a lapse of more than 30 days of having an active authorization.
Additional medication(s) are not being added to the continuation request.

Exclusion Criteria / Not Medically Necessary

Epkinly is not authorized when ANY of the following apply:

ANY of the following

Disease progression while taking Epkinly (epcoritamab-bysp).
Dosing exceeds single dose limit of Epkinly (epcoritamab-bysp) 48 mg.48 mg
Investigational use or off-label indication that is not supported by sufficient evidence or is not generally accepted by the medical community.
Sufficient evidence is defined by CMS-recognized compendia or acceptable peer-reviewed literature and includes considerations such as representation of patient/tumor characteristics, regimen representation, clinically meaningful outcomes (e.g., ASCO definitions: HR < 0.80 or OS/PFS benefit ≥ 3 months), appropriate experimental design, and that case reports/meeting abstracts without full peer-reviewed articles lack adequate support.

Safety / Required Monitoring

Warnings that affect continuation and administration decisions (operationally required monitoring/actions):

ALL of the following

CRS: Cytokine release syndrome (CRS) can occur; initiate treatment with the epcoritamab step-up dosage schedule to reduce incidence and severity; withhold epcoritamab until CRS resolves or permanently discontinue based on severity.
ICANS: Immune effector cell-associated neurotoxicity syndrome (ICANS) can occur; monitor patients for neurologic signs/symptoms; withhold epcoritamab until ICANS resolves or permanently discontinue based on severity.

Provider Actions & Prior Authorization

Prior Authorization

Prior authorization required via Evolent

Prior authorization is required. All medication requests for Epkinly must be processed by Evolent. Medications not authorized by Evolent may be deemed not approvable and therefore not reimbursable.

Documentation Required

Document prior therapies and transplant/CAR-T candidacy

When requesting Epkinly in combination with gemcitabine and oxaliplatin (GemOx), document the number and types of prior systemic therapies received, including exposure to an anti-CD20 monoclonal antibody, and document that the member is not a candidate for CAR T-cell therapy or transplant.

Applicable Codes

Drug HCPCS/J-codeHCPCSCovered

J9321

Injection, epcoritamab-bysp, 0.16 mg

Billing note: Epkinly is billed using HCPCS/J-code J9321 (Injection, epcoritamab-bysp, 0.16 mg); ensure per-dose reporting aligns with J-code units. The policy specifies a single-dose maximum of 48 mg; dosing that exceeds this single-dose limit is excluded. All medication requests for Epkinly must be processed and prior authorized by Evolent per the policy; medications not authorized by Evolent may be deemed not approvable and not reimbursable.

Clinical Evidence

Evidence and key references: Key trial evidence cited includes Brody JD et al., EPCORE NHL-2 trial reporting Epcoritamab plus GemOx in transplant-ineligible relapsed/refractory DLBCL (Blood 2025). Regulatory reference: Epkinly prescribing information (Genmab US, Inc. 2025). Policy accepts FDA product labeling and evidence from CMS-recognized compendia, NCCN, ASCO clinical guidelines, or peer-reviewed literature that meets CMS standards (Medicare Benefit Policy Manual Chapter 15) as sufficient for supported uses.

Optional quick metrics

Key trial - DLBCL (GemOx combo)Brody JD et al., Blood 2025; EPCORE NHL-2 trial

Key evidence - Follicular lymphomaFalchi L et al., Blood 2025 (fixed-duration epcoritamab + R2)

Supporting trial - Epcoritamab monotherapyLinton KM et al., Lancet Haematol 2024 (EPCORE NHL-1)

Regulatory/label sourceEpkinly prescribing information. Genmab US, Inc. 2025

Background & Definitions

Background: This policy establishes accepted uses for Epkinly (epcoritamab-bysp) including FDA-approved labeling and specified off-label indications supported by CMS-recognized compendia, NCCN, ASCO, or peer-reviewed literature that meets CMS standards. Evolent is responsible for processing all medication requests from network ordering providers and enforces utilization management, including prior authorization; medications not authorized by Evolent may be deemed not approvable and not reimbursable. Scope context: applies to medication requests processed by Evolent for the listed lines of business (Commercial, Exchange/Marketplace, Medicaid) and defines clinical indications, contraindications/warnings, exclusion criteria, coding, and utilization expectations.

Definitions: "Continuation request exemption": Continuation requests for a not-approvable medication shall be exempt from this Evolent policy provided the member has not experienced disease progression on the requested medication; the requested medication was used within the last year without a lapse of more than 30 days of having an active authorization; and additional medication(s) are not being added to the continuation request. "Sufficient evidence": Evidence supported by CMS-recognized compendia or acceptable peer-reviewed literature meeting criteria such as appropriate study design and clinically meaningful outcomes per ASCO.

Revision History

July 2024added

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

July 2025revised

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

December 2025revisedLatest

Updated DLBCL and Follicular Lymphoma indications and exclusion criteria; updated references.