Oncology Drug Reference Sheet: Epcoritamab-Bysp

August 20, 2024 by Madeline Johnston MSN, RN, OCN®

In May 2023, the U.S. Food and Drug Administration (FDA) announced it had granted accelerated approval (https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-epcoritamab-bysp-relapsed-or-refractory-diffuse-large-b-cell) for the first CD20 bispecific antibody drug, epcoritamab-bysp (Epkinly™) for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL). In June 2024, the FDA expanded the indication with accelerated approval (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-epcoritamab-bysp-relapsed-or-refractory-follicular-lymphoma) for the treatment of relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy.

This ONS resource was produced for educational purposes only. Refer to the full prescribing information (https://www.pi.amgen.com/-/media/Project/Amgen/Repository/pi-amgen-com/Imdelltra/imdelltra_fpi.pdf) for all details. 

DRUG INFORMATION
ClassificationBispecific CD20-directed CD3 T-cell engager
Mechanism of ActionAs a T-cell–engaging bispecific antibody, epcoritamab-bysp binds to the CD3 receptor on T-cells and binds to the CD20 receptor on the surface of lymphoma cells and healthy B-cells. This causes the release of cytokines and induces lysis of B-cells.
IndicationsEpcoritamab-bysp has accelerated approval for adult patients with relapsed or refractory FL after two or more lines of systemic therapy. Epcoritamab-bysp is also approved for relapsed or refractory DLBCL and high-grade B-cell lymphoma after two or more lines of systemic therapy.
ADMINISTRATION
Dosing, Frequency, and Administration 

This drug follows a step-up dosing schedule.

Treatment CycleTreatment DayEpcoritamab-Bysp Dose
DLBL or high-grade B-cell lymphomaCycle 11Step-up dose 10.16 mg
8Step-up dose 20.8 mg
15*Full dose48 mg
2248 mg
Cycles 2 and 31, 8, 15, and 2248 mg
Cycles 4–91 and 1548 mg
Cycles 10 and beyond148 mg
*Monitor patients for 24 hours following administration to assess for signs of cytokine release syndrome (CRS) and neurotoxicities.
FLCycle 11Step-up dose 10.16 mg
8Step-up dose 20.8 mg
15Step-up dose 33 mg
22First full dose48 mg
Cycles 2 and 31, 8, 15, and 2248 mg
Cycles 4–91 and 1548 mg
Cycles 10 and beyond148 mg
RouteSubcutaneous, preferably in the lower abdomen or the thigh. Alternate the injection site from left to right side.
Safe HandlingEpcoritamab-bysp is a potentially hazardous drug per the National Institute for Occupational Safety and Health (https://www.usp.org/compounding/general-chapter-hazardous-drugs-handling-healthcare#:~:text=The%20National%20Institute%20for%20Occupational,low%20doses%2C%20genotoxicity%2C%20or%20structure) definition. Follow safe handling precautions (https://www.ons.org/books/safe-handling-hazardous-drugs-third-edition).
ADVERSE REACTIONS
  • The major side effects include infections, neutropenia, thrombocytopenias, and other adverse reactions include:
    • CRS and infection
    • Pain and fatigue
    • Rash
    • Nausea, diarrhea, constipation, abdominal pain, and mucositis
    • Cough or dyspnea
    • Headache, neurologic changes, peripheral neuropathy and paresthesias, and dizziness
    • Insomnia
    • Renal insufficiency 
WARNINGS
  • Black box warnings: The package insert has a boxed warning for the risk of CRS and immune effector cell-associated neurotoxicity syndrome (ICANS).
  • Other warnings: Epcoritamab-bysp may cause fetal harm when administered to a pregnant individual. 
NURSING CONSIDERATIONS
Pretreatment
  • Consider Pneumocystis jirovecii pneumonia and herpes virus prophylaxis.
  • Ensure correct dose and premedication (as applicable) are ordered based on dosage schedules.
  • Administer recommended premedications to prevent the risk for CRS:
CyclePatients Requiring PremedicationPremedicationAdministration
Cycle 1All patients
  • Prednisolone (100 mg, oral or IV) or dexamethasone (15 mg, oral or IV) or equivalent
  • 30–120 minutes prior to each weekly administration
  • For 3 consecutive days following each weekly administration during cycle 1
  • Diphenhydramine (50 mg, oral or IV) or equivalent
  • Acetaminophen (650–1,000 mg oral)
  • 30–120 minutes prior to each weekly administration
Cycle 2 and beyondPatients who experienced grade 2 or 3 CRS with previous dose
  • Prednisolone (100 mg, oral or IV) or dexamethasone (15 mg, oral or IV) or equivalent
  • 30–120 minutes prior next administration of this drug after a Grade 2 or 3 CRS event
  • For 3 consecutive days following the next administration of this drug until it is given without subsequent CRS of grade 2 or higher
Note. Epcoritamab-bysp is permanently discontinued after grade 4 CRS.
Administration
  • Because of the risk for CRS and ICANS, monitor patients for:
    • Fever, hypotension, hypoxia, dyspnea, chills, and tachycardia
    • Headache, confusion, tremors, dizziness, and ataxia
    • Lethargy, tremor, dysgraphia, aphasia, and nonconvulsive status epilepticus
  • If you suspect CRS or ICANS, administer supportive therapy, which may require intensive care.
  • Because of the risk for CRS and neurotoxicities, monitor patients for 24 hours after administration of the first full dose of 48 mg on cycle 1, day 15.
  • Monitor the injection site for signs of reaction, including redness, bruising, or tenderness.
Post-Treatment
  • Observe and measure patients’ vital signs.
  • Understand any new treatment modifications based on patient response and adverse reactions.
  • Conduct a follow-up assessment for toxicities and manage any CRS and ICANS treatment according to grade.
  • Ensure patients have prescriptions for home symptom management and understand how to use them.
PATIENT EDUCATION
  • Inform patients about the risk for CRS, ICANS, embryo-fetal toxicities, cytopenias, and infection.
  • Teach patients about the symptoms associated with neurotoxicities and to avoid the operation of heavy machinery or driving until symptoms resolve.
  • Educate patients about the signs and symptoms of infection and when to contact their healthcare professional.
RESOURCES
Patient ResourcesPatient assistance program: Visit MyNavCare.com/patient (https://www.mynavcare.com/patient) or call 866-628-2271.
Healthcare Professional Resources
Other ResourcesNational Cancer Institute’s page for epcoritamab-bysp (https://www.cancer.gov/about-cancer/treatment/drugs/epcoritamab-bysp)
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