epcoritamab — Drug Monograph

Epcoritamab (Epkinly) — CD3xCD20 Bispecific for B-cell Lymphoma

Epcoritamab (Epkinly) is a subcutaneous CD3xCD20 bispecific antibody for relapsed or refractory B-cell lymphoma. It simultaneously engages CD20 on malignant B cells and CD3 on T cells, redirecting T-cell-mediated cytotoxicity against CD20-positive tumor cells, and is the only CD20xCD3 bispecific in lymphoma given subcutaneously. Because T-cell activation can trigger cytokine release syndrome (CRS), it uses a step-up dosing schedule. This monograph covers epcoritamab indications in relapsed/refractory DLBCL and follicular lymphoma, the CD3/CD20 dual-targeting mechanism, the subcutaneous step-up dosing schedule, and CRS monitoring.

Indications (FDA / NCCN)

• Relapsed/refractory large B-cell lymphoma (DLBCL NOS, HGBL, DLBCL from FL, PMBCL) after ≥2 prior lines (EPCORE NHL-1)
• Relapsed/refractory follicular lymphoma Grade 1–3A after ≥2 prior lines
• CD20-positive B-cell disease — no companion biomarker beyond histology

Dosing

• Subcutaneous step-up: 0.16 mg (C1D1) → 0.8 mg (C1D8) → 48 mg (C1D15)
• 48 mg SC weekly (Cycles 1–3), then Q2W (Cycles 4–9), then Q4W (Cycle 10+)
• Inject into the abdomen (preferred site); rotate sites
• Premedicate (antipyretic, antihistamine, corticosteroid) for first 3 doses

Monitoring

• Remain in a healthcare facility ≥24 h after the 0.16 mg and 0.8 mg step-up doses
• CRS signs/symptoms during and after step-up doses
• ICANS / neurologic toxicity
• CBC and for infections (including PJP / antiviral prophylaxis)

Brand names: Epkinly

Drug class: Other

Mechanism of Action

Full-length IgG1 CD20×CD3 bispecific antibody that engages CD20 on malignant B cells and CD3ε on T cells simultaneously, inducing T-cell-mediated cytotoxicity of CD20-positive tumor cells. Unlike fragment-based bispecifics, the full-length IgG format provides a longer half-life. Notable for being the only bispecific T-cell-engaging antibody in lymphoma administered subcutaneously.

FDA Indications

• Relapsed or refractory large B-cell lymphoma (LBCL), including DLBCL NOS, high-grade B-cell lymphoma, DLBCL arising from FL, and primary mediastinal large B-cell lymphoma, after ≥2 prior lines of systemic therapy (FDA approval May 2023, EPCORE NHL-1: 38.9% CR rate)
• Relapsed or refractory follicular lymphoma (FL) Grade 1–3A after ≥2 prior lines of systemic therapy including anti-CD20 monoclonal antibody and alkylating agent (FDA approval 2024)

Common Side Effects

• CRS (50%)
• Injection site reactions
• Fatigue
• Pyrexia
• Neutropenia
• Diarrhea
• Musculoskeletal pain
• Infection

Clinical Pearl

Epcoritamab is the only CD20×CD3 bispecific T-cell engaging antibody administered subcutaneously, which may improve patient convenience and reduce infusion-related burden. The extremely low 0.16 mg starting dose (300-fold below the therapeutic 48 mg dose) is specifically designed to prime T cells gradually and minimize the severity of CRS during initial exposure.

Related Therapies & Mechanisms

• Axicabtagene ciloleucel (Yescarta) — Other · Lymphoma
• Belinostat (Beleodaq) — Other · Lymphoma
• Bleomycin (Blenoxane) — Other · Lymphoma
• Brexucabtagene autoleucel (Tecartus) — Other · Lymphoma