U.S. Food and Drug Administration (FDA)-Approved Indications

Epkinly is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B–cell lymphoma (HGBL), after two or more lines of systemic therapy.

Compendial Uses

B-cell lymphomas:

Diffuse large B-cell lymphomas

High grade B-cell lymphomas

Histologic transformation of indolent lymphomas to diffuse large B-cell lymphoma

Human immunodeficiency virus (HIV)-related B-cell lymphomas

HIV-related diffuse large B-cell lymphoma

Primary effusion lymphoma

Human herpes virus type 8 (HHV8)-positive diffuse large B-cell lymphoma, not otherwise specified

Monomorphic post-transplant lymphoproliferative disorders

Epcoritamab-bysp is available as Epkinly (Genmab US, Inc.) and is bispecific antibody that activates T-cells by binding to the CD3 receptor expressed on the surface of T-cells and CD20 expressed on the surface of lymphoma cells. In vitro, this activation of T-cells resulted in the release of proinflammatory cytokines and death of CD20 B-cells (Genmab US, 2023).

Per the prescribing information, black box warnings for Epkinly, include:

Cytokine release syndrome (CRS), including serious or life-threatening reactions: Initiate treatment with the Epkinly step-up dosing schedule to reduce the incidence and severity of CRS. Withhold Epkinly until CRS resolves or permanently discontinue based on severity.

Immune effector cell-associated neurotoxicity syndrome (ICANS), including life-threatening and fatal reactions: Monitor patients for neurological signs or symptoms of ICANS during treatment. Withhold Epkinly until ICANS resolves or permanently discontinue based on severity.

According to the prescribing information, Epkinly carries the following warnings and precautions:

Infections: Can cause serious or fatal infections. Monitor patients for signs or symptoms of infection, including opportunistic infections, and treat appropriately.

Cytopenias: Monitor complete blood cell counts during treatment.

Embryo-fetal toxicity: May cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception.

Per the prescribing information for Epkinly, the most common (≥ 20%) adverse reactions are cytokine release syndrome, fatigue, musculoskeletal pain, injection site reactions, pyrexia, abdominal pain, nausea, and diarrhea. The most common Grade 3 to 4 laboratory abnormalities (≥ 10%) are decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, decreased hemoglobin, and decreased platelets.

On May 19, 2023, the U.S. Food and Drug Administration (FDA) granted accelerated approval to Epkinly (epcoritamab-bysp) for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after two or more lines of systemic therapy. The FDA approval was based on supporting data from the EPCORE NHL-1 study (FDA, 2023).

In the EPCORE NHL-1 study, an open-label, multi-cohort, multicenter, single-arm trial, Thieblemont et al. (2023) evaluated the efficacy of Epkinly (epcoritamab-bysp) in 157 patients with relapsed or refractory large B-cell lymphoma (LBCL) after two or more lines of systemic therapy. Epkinly monotherapy was administered via subcutaneous injection according to the following 28-day cycle schedule: 1) cycle 1: Epkinly 0.16 mg on day 1, 0.8 mg on day 8, 48 mg on days 15 and 22, 2) cycles 2-3: Epkinly 48 mg on days 1, 8, 15, and 22, 3) cycles 4-9: Epkinly 48 mg on days 1 and 15, and 4) cycles 10 and beyond: Epkinly 48 mg on day 1. Epkinly treatment continued until disease progression or unacceptable toxicity. The efficacy population was made up of 148 patients with relapsed or refractory DLBCL, not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after two or more lines of systemic therapy, including at least one anti-CD20 monoclonal antibody-containing therapy. The primary efficacy end point was overall response rate (ORR) determined by Lugano 2014 criteria, as assessed by an independent review committee. The ORR was 61% (95% confidence interval [CI]: 53, 69) with 38% of patients achieving complete responses. The median follow-up was 9.8 months among responders with an estimated median duration of response (DOR) of 15.6 months (95% CI: 9.7, not reached).

Note

: Requires Precertification:

Precertification of

epcoritamab-bysp (Epkinly)

is required of all Aetna participating providers and members in applicable plan designs. For precertification of epcoritamab-bysp (Epkinly),

call (866) 752-7021 (commercial), or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification . For Medicare Part B plans, call (866) 503-0857, or fax (844) 268-7263.

Criteria for Initial Approval

B-Cell Lymphomas

Aetna considers epcoritamab-bysp (Epkinly) medically necessary for treatment of B-cell lymphoma after at least 2 prior lines of systemic therapy when the member has partial response, no response, progressive, relapsed, or refractory disease with

any

of the following subtypes:

Diffuse large B-cell lymphoma (DLBCL);

or

High grade B-cell lymphoma;

or

Histologic transformation of indolent lymphoma to DLBCL;

or

HIV-related B-cell lymphoma including HIV-related DLBCL, primary effusion lymphoma, and HHV8-positive DLBCL, not otherwise specified when the requested medication is used as a single agent;

or

Monomorphic post-transplant lymphoproliferative disorder when the requested medication is used as a single agent.

Aetna considers all other indications as experimental and investigational.

Continuation of Therapy

Aetna considers continuation of epcoritamab-bysp (Epkinly) therapy medically necessary in members requesting reauthorization for an indication listed in Section I when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

Dosage and Administration

Epcoritamab-bysp is supplied as Epkinly in the following dosage forms and strengths:

Injection: 4 mg/0.8 mL in a single-dose vial. Dilute prior to use.

Injection: 48 mg/0.8 mL in a single-dose vial.

Epkinly is for subcutaneous injection only.

The recommended dosage schedule for Epkinly is noted in the table below. Administer Epkinly in 28-day cycles until disease progression or unacceptable toxicity.

Epkinly Dosage Schedule Cycle of Treatment Footnote1 * Day of Treatment Dose of Epkinly Cycle 1 1 Step-up dose 1 0.16 mg 8 Step-up dose 2 0.8 mg 15 First full dose 48 mg 22 48 mg Cycles 2 and 3 1, 8, 15, and 22 48 mg Cycles 4 to 9 1 and 15 48 mg Cycles 10 and beyond 1 48 mg Footnote1

*Cycle = 28 days

Refer to the full prescribing information for Epkinly for preparation and administration, dosage modifications, and management of adverse reactions.

Source: Genmab US, 2023