Epcoritamab-bysp (Epkinly)

Epcoritamab: EP-koh-RIH-tah-mab

Epkinly: ep-KIN-lee

Diffuse large B cell lymphoma (DLBCL)

Epkinly is approved for:

• Patients with diffuse large B-cell lymphoma (DLBCL), not otherwise specified, (including DLBCL arising from indolent lymphoma and high-grade B cell lymphoma) who have received at least two prior treatments for their disease, but whose cancer either did not respond to treatment or has since come back.

Limitations of use

Limitations: Epkinly should only be administered in a treatment center and by adequately trained healthcare professionals who can ensure proper monitoring and immediate management of side effects associated with the drug.
Age: The safety and efficacy of Epkinly in patients under 18 years of age have not been established.
Pregnancy/Breastfeeding: Epkinly is not recommended for use during pregnancy due to potential for harm to the fetus. Patients are advised to use contraception during treatment with Epkinly and for 4 months after the last dose of Epkinly. The risks associated with Epkinly during breastfeeding are not known and cannot be ruled out. Due to the potential for adverse reactions in the breastfed child, patients are advised not to breastfeed during treatment with Epkinly and for 4 months after the last dose of Epkinly. 
Interactions with other drugs: Dose adjustments may become necessary for patients treated with certain CYP substrates at the start of treatment with Epkinly.

Antibody therapy

• Bispecific antibody therapy

Targets:

• CD20 on B cells
• CD3 receptor on T cells

Epkinly is a “bispecific antibody”. Antibodies are molecules that can bind to a particular target molecule. Bispecific antibodies are artificially made in the laboratory and can bind to two different targets at the same time. Epkinly binds to:

• a molecule called CD20 on the surface of lymphoma cells and some healthy B cells. CD20 is present at much higher quantities on the surface of cancer cells than normal healthy cells.
• a molecule called CD3 on the surface of T cells – the primary immune cells involved in killing cancer cells. CD3 is part of the T cell receptor, which is critical to the function of the T cell and is involved in stimulating the T cell to become active.

Because Epkinly can bind to one molecule on lymphoma cells and another on T cells at the same time, it acts as a bridge and keeps the T cell in close contact with the cancer cell. By binding CD3 on the T cell, Epkinly also stimulates the T cell to become activated and kill the cell it is bound to. Bispecific antibodies that direct T cells to kill cancer cells by binding to both cells at the same time are known as bispecific T cell engagers (BiTEs).

Patients receive antifungal medication prior to starting treatment with Epkinly to prevent a certain form of pneumonia, and may receive antiviral medication to prevent herpes zoster (shingles) reactivation. About 2 hours to 30 minutes prior to receiving each dose of Epkinly in treatment cycle 1, patients receive several medications to help reduce the risk of cytokine release syndrome:

• A corticosteroid (prednisolone or dexamethasone)
• An antihistamine (diphenhydramine)
• A painkiller and fever reducer (acetaminophen)

In addition, the corticosteroid is given for three consecutive days following each dose of Epkinly in treatment cycle 1 and, if needed, 2 hours to 30 minutes before Epkinly administration and for three consecutive days following Epkinly administration in subsequent treatment cycles.

Patients should be well hydrated before they receive Epkinly, which is administered via an injection under the skin (subcutaneous injection) of the lower part of the abdomen or the thigh. During the first treatment cycle (a 28-day period), a low dose of Epkinly is administered on day 1, a second, slightly higher dose of Epkinly is given on day 8, and a full dose of Epkinly is administered on day 15 and day 22 of treatment cycle 1. During the second and third treatment cycles, a full dose of Epkinly is administered on days 1, 8, 15, and 22. During treatment cycles 4 to 9, a full dose of Epkinly is administered on days 1 and 15. For every subsequent treatment cycle, a full dose of Epkinly is given on day 1 only.

It is important to keep in mind that each patient’s outcome is individual and may be different from the results found in the clinical studies. In addition, immunotherapy can sometimes take several months to yield an observable treatment response.

Diffuse large B cell lymphoma

In a clinical study, 148 patients with diffuse large B-cell lymphoma (DLBCL), not otherwise specified, (including DLBCL arising from indolent lymphoma and high-grade B-cell lymphoma) who had received at least two prior treatments for their disease, but whose cancer either did not respond to treatment or had since come back, were treated with Epkinly. 

(For a definition of median click HERE.)

Epkinly targets CD20, which, while present on follicular lymphoma cells, is also present on some normal B cells. As a result, Epkinly can also kill normal B cells, increasing the risk of serious infections. Other common side effects of Epkinly include cytokine release syndrome, pain in the muscles, joints, and bones, fatigue, injection site reactions, fever, abdominal pain, nausea, diarrhea, low white blood cell count, low platelet count, and low hemoglobin levels in the blood. Some side effects, such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, infections, or abnormal blood counts, can become serious or life-threatening. Patients and caregivers receive careful instructions to monitor for signs and symptoms of side effects. These conditions are managed by the healthcare provider.

Cytokine release syndrome (CRS)
CRS is caused by a widespread release of molecules called cytokines, which can cause inflammation and can affect the function of various organs. Cytokines may be released by the T cells to which Epkinly binds, or by other immune cells in the patient’s body. Signs and symptoms of CRS include fever, low blood pressure, hypoxia (low oxygen levels), fast heartbeat rate, shortness of breath, and chills. CRS typically occurs within 24 hours after the most recent dose of Epkinly in treatment cycle 1. A healthcare provider should be immediately notified if symptoms occur.

Immune effector cell-associated neurotoxicity syndrome (ICANS)
Some of the cytokines released during CRS can result in disruption of the blood–brain barrier, leading to the development of neurological toxicities. ICANS typically occurs within 3 days after the most recent dose of Epkinly in treatment cycle 1. Symptoms of ICANS include shaking, lethargy, seizures, confusion, and difficulty with speech or handwriting. A healthcare provider should be immediately notified if symptoms occur.

For a more complete list of possible side effects, see the full prescribing information.

Manufacturer

Genmab US, Inc.

Approval

FDA 

Links to drug websites

• US: https://www.epkinly.com/

Last updated: May 22, 2023

This drug has not been approved in Europe.