Initial US Approval:
2023
Key Clinical Studies:
EPCORE FL-1 (Study M20-638; NCT05409066)
Drug Class/Description:
Bispecific CD20-directed CD3 T-cell engager
WARNING: CYTOKINE RELEASE SYNDROME and IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME
See full prescribing information for complete boxed warning.
Cytokine release syndrome (CRS), including serious or fatal reactions, can occur in patients receiving EPKINLY. Initiate treatment with the EPKINLY step-up dosage 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, can occur with EPKINLY. Monitor patients for neurological signs or symptoms of ICANS during treatment. Withhold EPKINLY until ICANS resolves or permanently discontinue based on severity.
Indications and Usage:
EPKINLY is a bispecific CD20-directed CD3 T-cell engager 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 after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
- In combination with lenalidomide and rituximab for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL).
- As monotherapy for the treatment of adult patients with relapsed or refractory FL after two or more lines of systemic therapy.
Dosage and Administration:
- For subcutaneous injection only.
- Recommended Dosage:
DLBCL and High-grade B-cell Lymphoma
| Cycle a | Day | 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 | |
| Cycle 10 and beyond | 1 | 48 mg | |
a Cycle = 28 days
EPKINLY as Monotherapy for FL
| Cycle a | Day | Dose of EPKINLY | |
|---|---|---|---|
| Cycle 1 | 1 | Step-up dose 1 | 0.16 mg |
| 8 | Step-up dose 2 | 0.8 mg | |
| 15 | Step-up dose 3 | 3 mg | |
| 22 | First full dose | 48 mg | |
| Cycles 2 and 3 | 1, 8, 15 and 22 | 48 mg | |
| Cycles 4 to 9 | 1 and 15 | 48 mg | |
| Cycle 10 and beyond | 1 | 48 mg | |
a Cycle = 28 days
EPKINLY in Combination with Lenalidomide and Rituximab for FL
| Cycle a | Day | Dose of EPKINLY | |
|---|---|---|---|
| Cycle 1 | 1 | Step-up dose 1 | 0.16 mg |
| 8 | Step-up dose 2 | 0.8 mg | |
| 15 | Step-up dose 3 | 3 mg | |
| 22 | First full dose | 48 mg | |
| Cycles 2 and 3 | 1, 8, 15, and 22 | 48 mg | |
| Cycles 4 to 12 | 1 | 48 mg | |
a Cycle = 28 days
- Monitor all patients for signs and symptoms of CRS and ICANS.
- Patients with DLBCL or high-grade B-cell lymphoma should be hospitalized for 24 hours after administration of the Cycle 1 Day 15 dosage of 48 mg.
- For patients with FL, assess whether hospitalization or outpatient monitoring is appropriate after administration of the Cycle 1 Day 22 dosage of 48 mg.
- Administer premedications, post-medications, and prophylaxis as recommended.
- Dosages of EPKINLY 0.16 mg and 0.8 mg require dilution prior to administration.
- See Full Prescribing Information for instructions on preparation and administration.
Dosage Forms and Strengths:
- Injection: 4 mg/0.8 mL in a single-dose vial.
- Injection: 48 mg/0.8 mL in a single-dose vial.
Contraindications:
None.
Warnings and Precautions:
- Infections: Can cause fatal or serious 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.
Adverse Reactions:
EPKINLY as monotherapy for LBCL or FL: The most common (≥ 20%) adverse reactions are CRS, injection site reactions, fatigue, musculoskeletal pain, fever, diarrhea, COVID-19, rash and abdominal pain. The most common Grade 3 to 4 laboratory abnormalities (≥ 10%) are decreases in lymphocyte count, neutrophil count, hemoglobin, and platelets.
EPKINLY in combination with lenalidomide and rituximab for FL: The most common (≥ 20%) adverse reactions are rash, upper respiratory tract infections, fatigue, injection site reactions, constipation, diarrhea, CRS, pneumonia, COVID-19, and fever. The most common Grade 3 to 4 laboratory abnormalities (≥ 10%) are decreased neutrophil count, lymphocyte count, and platelets.
Use in Specific Populations:
Lactation: Advise not to breastfeed.
Adapted From:
https://www.genmab-pi.com/prescribing-information/epkinly-pi.pdf
Every health-care provider should make their own determination regarding specific safe and appropriate patient care practices, including drug dosages and indications. The provider should always consult the most recent prescribing/product information. FDA Focus information is not guaranteed to be accurate, complete, or current. JADPRO and its editors, authors, reviewers, and commentators cannot be held responsible for any liability incurred as a consequence of the application of any of the information listed within.
