MHN Epkinly (epcoritamab) Coverage Update

Coverage and Medical Necessity Criteria

Initial Therapy Criteria

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

Initial Approval for B-Cell Lymphomas: 1) Diagnosis of one of the following: a) DLBCL (see Appendix D for subtypes); b) Classic follicular lymphoma (grades 1, 2, or 3A); c) Histologic transformation of follicular or marginal zone lymphoma to DLBCL (off-label); d) HIV-related B-cell lymphoma (off-label); e) Post-transplant lymphoproliferative disorder (off-label). 2) Prescribed by or in consultation with an oncologist or hematologist. 3) Age ≥ 18 years. 4) One of the following: a) For DLBCL: all of the following i) prescribed in combination with GemOx (gemcitabine + oxaliplatin); ii) member has received ≥ 1 line of systemic therapy; iii) member has relapsed or refractory disease OR relapsed < 12 months after completion of first-line therapy or primary refractory disease in non-candidates for CAR T-cell therapy OR relapsed > 12 months after first-line therapy if there is no intention to proceed to transplant; OR b) Member has received ≥ 2 lines of systemic therapy, had partial/no response/progressive/relapsed/refractory disease after prior systemic therapy, and Epkinly is prescribed as a single agent. 5) Dosing requirements: a) Cycle 1 step-up doses must not exceed 0.16 mg on day 1 and 0.8 mg on day 8 (for FL an additional step-up dose of 3 mg on day 15); b) Step-up may use up to three 4 mg/0.8 mL vials as appropriate; c) Full dose 48 mg per administration as per dosing schedule by cycle.

Approval duration: Medicaid/HIM 6 months; Commercial 6 months or to member renewal date.

Continuation Therapy Criteria

Covered for continuation when ALL of the following are met:

Continuation Therapy: 1) Member is currently receiving Epkinly via the Centene benefit, or documentation supports current receipt for a covered indication and at least 30 days of therapy. 2) Member is responding positively to therapy. 3) If the request is for a dose increase, one of the following applies: a) the new dose does not exceed 48 mg per dose; or b) the new dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).

Approval duration: Medicaid/HIM 12 months; Commercial 6 months or to member renewal date.

Dosing and Indication Coverage

Covered when administered per dosing regimens for approved indications and NCCN-supported uses:

DLBCL dosing regimen: For DLBCL: Administer in 28-day cycles until disease progression or unacceptable toxicity. Cycle 1: Day 1 step-up 0.16 mg SC; Day 8 step-up 0.8 mg SC; Day 15 first full dose 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 and beyond day 1: 48 mg SC.

Exact dosing schedule from policy (Section V).

Follicular lymphoma (FL) dosing regimen: For FL: Administer in 28-day cycles until disease progression or unacceptable toxicity. Cycle 1: Day 1 step-up 0.16 mg SC; Day 8 step-up 0.8 mg SC; Day 15 step-up 3 mg SC; Day 22 first full dose 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 and beyond day 1: 48 mg SC.

Exact dosing schedule from policy (Section V).

NCCN-supported later-line combination: Per NCCN Compendium, use in second-line and subsequent therapy in combination with gemcitabine and oxaliplatin (GemOx) is supported.

Referenced as an added NCCN-supported use in policy updates.

Requests for use of epcoritamab-bysp (Epkinly) for non‑FDA approved indications not specifically addressed in this policy are excluded unless the provider submits sufficient documentation demonstrating efficacy and safety in accordance with the payer's off‑label use policies (e.g., CP.CPA.09 for commercial, HIM.PA.154 for marketplace, CP.PMN.53 for Medicaid) or other applicable evidence of coverage documents.

The inclusion or exclusion of procedure, diagnosis, or billing codes in this policy is provided for information only. Coverage is contingent on the terms of this clinical policy and applicable state and federal requirements; providers must follow current coverage documents and regulatory rules when submitting claims.

Coding lists in this clinical policy are informational and do not constitute a guarantee of payment. Inclusion or exclusion of any code does not guarantee coverage; providers should verify up‑to‑date professional coding guidance prior to claim submission.

Billing and Coding

Referenced HCPCS CodesHCPCS

J9321

Injection, epcoritamab-bysp, 0.16 mg

Cycle length

Cycle length28-day cycles until disease progression or unacceptable toxicity

Cycle structureCycle 1 includes step-up and multiple weekly doses (days 1,8,15,22); later cycles reduce frequency per regimen

Use across indicationsSame 28-day cycle length used for both DLBCL and follicular lymphoma dosing regimens

Provider Responsibilities and Authorization

Prior Authorization

Prior Authorization Required

Prior authorization required. Approval is contingent upon meeting all initial criteria and submission of required documentation supporting medical necessity.

Prior authorization required prior to initiation of therapy
Approval contingent on meeting the Initial Approval Criteria in Section I

Documentation Required

Required Documentation

Provider must submit documentation (such as office chart notes, lab results, imaging, pathology reports, and other clinical information) that demonstrates the member meets all approval criteria. Lack of sufficient documentation may result in denial.

Include relevant office notes, diagnostic test results, prior therapy records, and consult notes from the prescribing oncologist/hematologist
Document rationale for off‑label use when applicable (see below)

Definitions and Safety Notices

Epcoritamab-bysp (Epkinly) is a bispecific CD20-directed CD3 T‑cell engager indicated for adult patients with relapsed or refractory diffuse large B‑cell lymphoma (DLBCL) and relapsed or refractory follicular lymphoma (FL) after prior systemic therapy. Dosing is administered subcutaneously in 28‑day cycles with a recommended Cycle 1 step‑up schedule followed by a 48 mg full dose per the dosing regimen specified in the policy. The product carries boxed warnings for cytokine release syndrome and immune effector cell‑associated neurotoxicity syndrome (ICANS). Provider resources and dosing details, including vial sizes and the HCPCS code J9321, are referenced in the policy and supporting prescribing information.

Epcoritamab-bysp (Epkinly)

AgentEpcoritamab-bysp (Epkinly)

Mechanism of actionBispecific CD20-directed CD3 T-cell engager

Route and formulationSubcutaneous administration; step-up dosing in Cycle 1 followed by 48 mg maintenance doses

DLBCL subtypes

Line-of-Therapy Specific Criteria

second-line | third-line (per scenario)

Line of therapy rules: - For follicular lymphoma (FL): indicated after ≥ 2 lines of systemic therapy. - For DLBCL: allowed in specific scenarios as follows: when used in combination with GemOx after ≥ 1 line of systemic therapy for relapsed/refractory disease or specified relapse timing relative to first-line therapy and transplant/CAR-T candidacy; OR after ≥ 2 lines of systemic therapy as a single agent when prior therapy resulted in partial/no response, progression, relapse, or refractory disease.

second-line

Second-line and subsequent therapy: Per NCCN Compendium, use in second-line and subsequent therapy in combination with gemcitabine and oxaliplatin (GemOx) is supported.

Added to policy per 3Q 2025 annual review.

Dosing Schedules and Regimens

Regimen	Indication / Notes	Coverage Status
Epkinly (epcoritamab-bysp) given in combination with gemcitabine + oxaliplatin (GemOx)	For DLBCL: permitted when member meets DLBCL-specific criteria (see policy) including prior lines of therapy and relapse/refractory timing; use per NCCN-supported later-line combination guidance.	Combination with GemOx for specified DLBCL scenarios
Epkinly (epcoritamab-bysp) as a single-agent	Permitted as monotherapy when member meets single-agent criteria (e.g., ≥2 prior systemic therapies or other criteria per policy).	Single-agent per criteria

Dosing Element	Cycle 1 Step-up / Early Doses	Notes
Day 1 (Cycle 1)	0.16 mg subcutaneous	Step-up dose 1; must not exceed 0.16 mg.
Day 8 (Cycle 1)	0.8 mg subcutaneous	Step-up dose 2; must not exceed 0.8 mg.
Day 15 (Cycle 1) — follicular lymphoma only	3 mg subcutaneous	FL-specific third step-up dose prior to first full 48 mg dose.
Post step-up / Full dosing	48 mg subcutaneous per full-dose administration	Use one 48 mg vial per full dose; step-up may use up to three 4 mg/0.8 mL vials as appropriate.

Regimen / Use	Cycle 1 Step-up	Maintenance / Subsequent Dosing	Notes / Coverage Context
DLBCL — monotherapy dosing regimen	Day 1: 0.16 mg SC; Day 8: 0.8 mg SC; Day 15: 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	Administer in 28-day cycles until progression or unacceptable toxicity; coverage when administered per dosing regimens for approved indications.
Follicular lymphoma — monotherapy dosing regimen	Day 1: 0.16 mg SC; Day 8: 0.8 mg SC; Day 15: 3 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	FL indication included per updated prescribing information; step-up schedule differs (3 mg on day 15).
NCCN-supported later-line combination: Epkinly + gemcitabine + oxaliplatin	Cycle 1 step-up dosing as above (DLBCL or FL per indication)	Maintenance 48 mg dosing per schedule above	Per NCCN Compendium (policy update), use in second-line and subsequent therapy in combination with gemcitabine and oxaliplatin is supported; coverage added accordingly.

OpenPayer

Clinical Policy: Epcoritamab-bysp (Epkinly)