Chapter 1: Introduction
The purpose of this video is to provide information on EPKINLY, epcoritamab-bysp, product handling and instructions for dilution.
On screen legal disclaimer – No voiceover narration.
Your role in preparing EPKINLY is vital to patients and their care partners as key members of their care team.
The recommended doses for EPKINLY include a 0.16 mg dose (step-up dose 1), a 0.8 mg dose (step-up dose 2) and a 48 mg dose (full dose).
EPKINLY is administered according to the following 28-day dosing cycles until disease progression or unacceptable toxicity.
Please see Important Safety Information, including Boxed Warnings for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), at the end of this video.
Availability of product and premedications should be verified by staff when planning the patient’s treatment schedule.
Herein, we will give detailed instructions on how to properly store and handle EPKINLY.
Storage and Handling
Before the dilution and preparation of EPKINLY:
Store EPKINLY refrigerated at 2 to 8 degrees Celsius (36 to 46 degrees Fahrenheit)
Keep EPKINLY in the original carton to protect from light
Use the diluted EPKINLY solution immediately
- If not used immediately, store the solution
- Refrigerated at 2 to 8 degrees Celsius (36 to 46 degrees Fahrenheit) for up to 24 hours or
- At room temperature at 20 to 25 degrees Celsius (68 to 77 degrees Fahrenheit) for up to 12 hours
- The total storage time from the start of dose preparation to administration should not exceed 24 hours
- Protect EPKINLY from direct sunlight
- Allow EPKINLY solution to equilibrate to room temperature for no more than 1 hour before administration
- Discard unused EPKINLY solution beyond the allowable storage time
Now that you know how to properly store and handle EPKINLY, lets go over how to properly prepare EPKINLY for administration into your patients.
Product Preparation
EPKINLY is for subcutaneous injection only.
This video will provide step-by-step instructions for safely preparing EPKINLY using an empty sterile vials method.
Note: Certain doses of EPKINLY require dilution prior to administration. Follow the preparation instructions provided in this video and the full prescribing information, as improper preparation may lead to improper dose.
Chapter 2: 0.16 mg Dose (Step-up Dose 1)
Here we will go through the necessary steps needed to prepare the EPKINLY 0.16 mg dose.
Let's begin by preparing your 0.16 mg dose dilution supplies.
Here is a compilation of all supplies you will need to assemble before you get started.
Now we will go through a simulation on how to prepare a 0.16 mg dose of EPKINLY using empty sterile vials.
To prepare the 0.16 mg dose, EPKINLY 4 mg/0.8 mL requires TWO dilutions.
Filtration of the diluted solution is not required.
When diluting EPKINLY, use an appropriately sized, syringe, vial, and needle for each transfer step.
First, grab your two appropriately sized empty sterile vials and label the first empty vial “Dilution A”.
Next, label your second empty vial “Dilution B”.
Grab the 4 mg/0.8 mL EPKINLY vial with the turquoise cap that is now at room temperature.
Gently swirl the EPKINLY vial. DO NOT invert, vortex, or vigorously shake the vial.
In order to maintain aseptic technique, swab the EPKINLY vial 3 times in the same direction with an alcohol swab.
Alternatively, the EPKINLY vial can also be sprayed with alcohol and allowed to dry before starting the dilution process.
This aseptic technique will be repeated several times throughout the dilution process.
Withdraw 0.8 mL of EPKINLY.
Note: It is important to remove all bubbles using proper technique to ensure that you are drawing up the appropriate volume of EPKINLY.
Transfer the 0.8 mL of EPKINLY into the Dilution A vial.
The EPKINLY vial is no longer needed and may be discarded.
REMINDER: Once you have pierced an empty vial, you have equalized the pressure within that vial, so for compounding practices, you need to make sure that you maintain negative pressure within the vial.
Grab one vial of 0.9% Sodium Chloride for injection.
Withdraw 4.2 mL of 0.9% Sodium Chloride.
Transfer 4.2 mL of 0.9% Sodium Chloride into the Dilution A vial.
Gently swirl the Dilution A vial for 30–45 seconds.
Next, grab the second empty vial labeled “Dilution B”.
Withdraw 2 mL of solution from the Dilution A vial.
Transfer 2 mL of solution from the Dilution A vial into the Dilution B vial.
The Dilution A vial is no longer needed and can be discarded.
Grab your second vial of 0.9% Sodium Chloride for injection.
Withdraw 8 mL of 0.9% Sodium Chloride.
Transfer 8 mL of 0.9% Sodium Chloride into the Dilution B vial to make a final concentration of 0.16 mg/mL.
Gently swirl the Dilution B vial for 30–45 seconds.
Withdraw 1 mL of the solution from the Dilution B vial into a syringe intended for subcutaneous injection into the patient.
Label the syringe with the dose strength, 0.16 mg, and the time of day.
The syringe is now ready to be administered to the patient.
REMINDER:
- EPKINLY is for subcutaneous injection ONLY
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit
- Each vial will be a “single-dose” vial, meaning multiple doses must not be withdrawn from one vial
- After preparing each dose, discard the single-dose vial and any unused portion of EPKINLY
Chapter 3: 0.8 mg Dose (Step-up Dose 2)
Here we will go through the necessary steps needed to prepare the EPKINLY 0.8 mg dose.
Let’s begin by preparing your 0.8 mg dose dilution supplies.
Here is a compilation of all supplies you will need to assemble before you get started.
Now we will go through a simulation on how to prepare a 0.8 mg dose of EPKINLY using empty sterile vials.
To prepare the 0.8 mg dose, EPKINLY 4 mg/0.8 mL requires ONE dilution.
Filtration of the diluted solution is not required.
When diluting EPKINLY, use an appropriately sized, syringe, vial, and needle for each transfer step.
First, grab your appropriately sized empty sterile vial and label the empty vial “Dilution A”.
Grab the 4 mg/0.8 mL EPKINLY vial with the turquoise cap that is now at room temperature.
Gently swirl the EPKINLY vial. DO NOT invert, vortex, or vigorously shake the vial.
In order to maintain aseptic technique, swab the EPKINLY vial 3 times in the same direction with an alcohol swab.
Alternatively, the EPKINLY vial can also be sprayed with alcohol and allowed to dry before starting the dilution process.
This aseptic technique will be repeated several times throughout the dilution process.
Withdraw 0.8 mL of EPKINLY.
Note: It is important to remove all bubbles using proper technique to ensure that you are drawing up the appropriate volume of EPKINLY.
Transfer the 0.8 mL of EPKINLY into the Dilution A vial.
The EPKINLY vial is no longer needed and can be discarded.
REMINDER: Once you have pierced an empty vial, you have equalized the pressure within that vial, so for compounding practices, you need to make sure that you maintain negative pressure within this vial.
Grab your vial of 0.9% Sodium Chloride for injection.
Withdraw 4.2 mL of 0.9% Sodium Chloride.
Transfer 4.2 mL of 0.9% Sodium Chloride into the Dilution A vial to make a final concentration of 0.8 mg/mL.
Gently swirl the Dilution A vial for 30–45 seconds.
Withdraw 1 mL of the solution from the Dilution A vial into a syringe intended for subcutaneous injection into the patient.
Label the syringe with the dose strength, 0.8 mg, and the time of day.
The syringe is now ready to be administered to the patient.
REMINDER:
- EPKINLY is for subcutaneous injection ONLY
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit
- Each vial will be a “single-dose” vial, meaning multiple doses must not be withdrawn from one vial
- After preparing each dose, discard the single-dose vial and any unused portion of EPKINLY
Chapter 4: 48 mg Dose (Full Dose)
Lastly, we will go through the necessary steps needed to prepare the EPKINLY 48 mg dose.
Let’s begin by preparing your 48 mg dose supplies.
Here is a compilation of all supplies you will need to assemble before you get started.
Here we will go through a simulation on how to prepare a 48 mg dose of EPKINLY.
First, grab your 48 mg/0.8 mL EPKINLY vial with the orange cap that is now at room temperature.
Gently swirl the EPKINLY vial. DO NOT invert, vortex, or vigorously shake the vial.
In order to maintain aseptic technique, swab the EPKINLY vial 3 times in the same direction with an alcohol swab.
Alternatively, the EPKINLY vial can also be sprayed with alcohol and allowed to dry.
Withdraw 0.8 mL of EPKINLY into a syringe intended for subcutaneous injection into the patient.
Note: It is important to remove all bubbles using proper technique to ensure that you are drawing up the appropriate volume of EPKINLY.
Label the syringe with the dose strength, 48 mg, and the time of day.
The syringe is now ready to be administered to the patient.
REMINDER:
- EPKINLY is for subcutaneous injection ONLY
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit
- Each vial will be a “single-dose” vial, meaning multiple doses must not be withdrawn from one vial
- After preparing each dose, discard the single-dose vial and any unused portion of EPKINLY
Chapter 5: Indication & Important Safety Information
INDICATION
EPKINLY is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma (HGBL) after 2 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).
IMPORTANT SAFETY INFORMATION
BOXED WARNINGS
- Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving EPKINLY. 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, 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.
Cytokine Release Syndrome (CRS)
- EPKINLY can cause CRS, including serious or life-threatening reactions. CRS occurred in 51% of patients at the recommended dose in the clinical trial (37% grade 1, 17% grade 2, and 2.5% grade 3). Recurrent CRS occurred in 16% of patients. Of all the CRS events, most (92%) occurred during cycle 1. In cycle 1, 9% of CRS events occurred after the 0.16 mg dose (cycle 1, day 1), 16% after the 0.8 mg dose (cycle 1, day 8), 61% after the 48 mg dose (cycle 1, day 15), and 6% after the 48 mg dose (cycle 1, day 22). The median time to onset of CRS from the most recently administered EPKINLY dose across all doses was 24 hours (range, 0-10 days). The median time to onset after the first full 48 mg dose was 21 hours (range, 0-7 days). CRS resolved in 98% of patients; the median duration of CRS events was 2 days (range, 1-27 days).
- Signs and symptoms of CRS can include pyrexia, hypotension, hypoxia, dyspnea, chills, and tachycardia. Concurrent neurological adverse reactions associated with CRS occurred in 2.5% of patients and included headache, confusional state, tremors, dizziness, and ataxia.
- Initiate EPKINLY according to the step-up dosing schedule. Administer pretreatment medications to reduce the risk of CRS and monitor patients for potential CRS. Following administration of the first 48 mg dose, patients should be hospitalized for 24 hours. At the first signs or symptoms of CRS, immediately evaluate patients for hospitalization, manage per current practice guidelines, and administer supportive care as appropriate. Withhold or discontinue EPKINLY based on the severity of CRS.
- Patients who experience CRS (or other adverse reactions that impair consciousness) should be evaluated and advised not to drive and to refrain from operating heavy or potentially dangerous machinery until resolution.
Immune Effector Cell–Associated Neurotoxicity Syndrome (ICANS)
- EPKINLY can cause life-threatening and fatal ICANS. ICANS occurred in 6% (10/157) of patients in the clinical trial (4.5% grade 1, 1.3% grade 2, 0.6% fatal: 1 event). Of the 10 ICANS events, 9 occurred in cycle 1 of treatment. The median time to onset was 16.5 days (range, 8-141 days) from the start of treatment. Relative to the most recent administration, the median time to onset was 3 days (range, 1-13 days). The median duration of ICANS was 4 days (range, 0-8 days), with ICANS resolving in 90% of patients with supportive care.
- Signs and symptoms of ICANS can include confusional state, lethargy, tremors, dysgraphia, aphasia, and nonconvulsive status epilepticus. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.
- Monitor for potential ICANS. At the first signs or symptoms of ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold or discontinue EPKINLY per recommendations and consider further management per current practice guidelines.
- Patients who experience signs or symptoms of ICANS or any other adverse reactions that impair cognition or consciousness should be evaluated, including potential neurology evaluation, and patients at increased risk should be advised not to drive and to refrain from operating heavy or potentially dangerous machinery until resolution.
Infections
- EPKINLY can cause serious and fatal infections. In the clinical trial, serious infections, including opportunistic infections, were reported in 15% of patients treated with EPKINLY at the recommended dose (14% grade 3 or 4, 1.3% fatal). The most common grade 3 or greater infections were sepsis, COVID-19, urinary tract infection, pneumonia, and upper respiratory tract infection.
- Monitor patients for signs and symptoms of infection prior to and during treatment with EPKINLY and treat appropriately. Avoid administration of EPKINLY in patients with active infections.
- Prior to starting EPKINLY, provide Pneumocystis jirovecii pneumonia (PJP) prophylaxis and consider prophylaxis against herpes virus.
- Withhold or consider permanent discontinuation of EPKINLY based on severity.
Cytopenias
- EPKINLY can cause serious or severe cytopenias, including neutropenia, anemia, and thrombocytopenia. Among patients who received the recommended dose in the clinical trial, grade 3 or 4 events occurred in 32% (decreased neutrophils), 12% (decreased hemoglobin), and 12% (decreased platelets). Febrile neutropenia occurred in 2.5%.
- Monitor complete blood counts throughout treatment. Based on severity of cytopenias, temporarily withhold or permanently discontinue EPKINLY. Consider prophylactic granulocyte colony-stimulating factor administration as applicable.
Embryo-Fetal Toxicity
- EPKINLY may cause fetal harm. Advise pregnant women of the potential risk to the fetus. Verify pregnancy status in females of reproductive potential prior to initiating EPKINLY. Advise females of reproductive potential to use effective contraception during treatment with EPKINLY and for 4 months after the last dose.
Adverse Reactions
- The most common (≥20%) adverse reactions were CRS, fatigue, musculoskeletal pain, injection site reactions, pyrexia, abdominal pain, nausea, and diarrhea. The most common grade 3 to 4 laboratory abnormalities (≥10%) were decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, decreased hemoglobin, and decreased platelets.
Lactation
- Advise women not to breastfeed during treatment and for 4 months after the last dose of EPKINLY.
Please see accompanying full Prescribing Information or visit www.EPKINLYHCP.com.
