Dosing & administration
EPKINLY is administered subcutaneously1
Learn about the steps involved:
Hospitalization is not required for monitoring with EPKINLY administration. Assess each patient.1
- Due to the risk of CRS and ICANS, monitor all patients for signs and symptoms
- Assess whether hospitalization or outpatient monitoring for the first 48 mg dose is appropriate based on comorbidities or other situational factors
- During outpatient monitoring after the first 48 mg dose, patients should remain in proximity to a healthcare facility that can assess and manage CRS
- Hospitalization may be needed to manage select adverse reactions
Please see Dosing for full context within respective indication links above or section 2 of the Prescribing Information.
Watch expert guidance for operationalizing EPKINLY
Hear key considerations to help your organization effectively onboard EPKINLY.
Prior to Administration
Dr. Graff: Hi everyone, and welcome to the program. I’m Dr Tara Graff, Bispecific Lead and Medical Oncologist at Mission Cancer and Blood where I also serve as Director of Clinical Trials. The objective of this presentation is to discuss key considerations for clinics onboarding EPKINLY.
VO: SELECT IMPORTANT SAFETY INFORMATION
INDICATIONS
DLBCL and High-grade B-cell Lymphoma
- EPKINLY is indicated for the treatment of adults 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 (HGBCL) 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 confirmatory trial(s).
Follicular Lymphoma
- EPKINLY is indicated in combination with lenalidomide and rituximab for the treatment of adults with relapsed or refractory follicular lymphoma (FL).
- EPKINLY is indicated as monotherapy for the treatment of adults with relapsed or refractory FL after 2 or more lines of systemic therapy.
BOXED WARNINGS
- 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.
Please continue watching to the end of the video for additional important safety information.
Dr. Graff: Joining me for this program is Dr Matt Chui. Welcome, Matt. Please introduce yourself for our audience.
Dr. Chui: Thanks, Tara. Hi, my name is Matthew Chui. I am the Clinical Oncology Pharmacy Manager at the University of Miami Sylvester Comprehensive Cancer Center. My clinical background is in lymphoma, which has been my clinical area of expertise for the past 6 years.
Dr. Graff: It’s a pleasure to have you. In this section, we will be discussing some important considerations prior to administration of EPKINLY. First and foremost, there must be a bispecific champion and team. This can look different depending on the size of your clinic, but this is crucial given the operational complexities associated with onboarding bispecifics, such as EPKINLY.
It’s important that the bispecific champion and team have clinical experience and members who can be a pharmacist, advanced practice provider, lead clinic nurse, and at least 1 physician in order to understand and implement the operational workflows and coordination of a multidisciplinary team. This includes concise, clear communication and collaboration across care teams that are administering bispecific antibodies.
The role also requires being capable of developing a network of other experienced champions, overseeing development of protocols, ensuring practice employees are sufficiently trained and educated on the nuances of bispecific antibody therapies, and coordinating patient transitions and administration strategies.
Matt, what are some of the other considerations clinics should keep in mind?
Dr. Chui: Well, Tara, some key considerations include engaging appropriate departments to add EPKINLY to existing processes and encouraging pharmacy, revenue cycle, and finance departments to add a new drug to your formulary.
So, for example, the pharmacy department would need to review the full Prescribing Information, Medication Guide, Dose Preparation Video, and Dosing and Administration Guide to familiarize themselves with EPKINLY preparation and administration.
Once they determine how providers order the medication, they may create an electronic treatment plan or paper order form to facilitate medication ordering by providers. The pharmacy department would also need to acquire appropriate medical supplies, following typical processes for product ordering and required equipment, such as empty sterile vials.
With regard to the revenue cycle or finance department, they would need to confirm that payer contracts are in place for EPKINLY. For billing and coding department, they would need to review EPKINLY-specific billing, coding, and coverage information. Clinics may want to consider enrolling patients in MyNavCare Patient Support, which is offered by the manufacturer for support with benefits and coverage, such as benefit verification and prior authorization for healthcare provider office, as well as copay assistance for eligible patients.
Some important points to highlight to key stakeholders include the following:
- EPKINLY now has a permanent J code since it has been on the market for over 2.5 years.
- The majority of doses, if not all, are given in the outpatient setting on a weekly, biweekly, or monthly basis. Flexibility for modalities such as an observation stay in lieu of an inpatient admission may allow to further optimize outpatient billing to avoid inpatient DRG payment models.
- Although EPKINLY is a T-cell engaging therapy, the reimbursement is vastly different than cellular therapy, where it is usually a one lump sum payment of roughly $400,000 to $500,000. And pharmacies should also take into consideration billing for waste for step-up doses, as they are given in a small amount of drug in comparison to the full dose where the entire vial of medication is given.
When it comes to safe administration of EPKINLY, it’s important for clinics to have a protocol, such as a protocol for management of CRS or ICANS, and order sets in place.
Multiple order sets for the various EPKINLY regimens for 3L + DLBCL or HGBCL and 2L + and 3L + FL will help with variations in schedule and step-up dosing for instance.
Here are a few things to keep in mind.
Following your policies regarding product ordering and procedures for onboarding new medications.
Utilize the bispecific champion or team to oversee the development of a protocol for EPKINLY.
Depending on your institution, a bispecific champion may look different. For instance, there could be one champion for EPKINLY or lymphoma, there could be an overall bispecific champion. This champion could be a physician, pharmacist, or nurse practitioner, or there could be a bispecific committee as well.
And as mentioned before, consider adding EPKINLY to your EHR system to further support its safe use in patients with 3L + DLBCL or HGBCL and 2L + and 3L + FL.
Please reach out to your AbbVie or Genmab representative for EPKINLY order sets.
Provide routine education on dose preparation, administration, and adverse event management, as well as EPKINLY clinical updates to staff who may see patients in the emergency room, urgent care, or hospital.
Communicate information about all potential adverse events, inclusive of serious adverse reactions for EPKINLY, as well as how to monitor and manage for CRS, ICANS, infections, and cytopenia.
If available, clinics should utilize their electronic health record systems to alert providers who enter the patient’s chart that the patient is receiving a bispecific antibody and is at risk for CRS and/or neurotoxicity.
In addition, call center staff may benefit from receiving education on how to triage symptoms promptly and appropriately.
Be sure to determine if satellite sites within the network will be administering EPKINLY and provide education on patient management.
Notify your Genmab or AbbVie EPKINLY representative of any product information or in-service needs at the local hospital, including information about appropriate management of all potential adverse reactions, inclusive of serious adverse reactions, as well as how to monitor for and manage CRS, ICANS, infections, and cytopenia.
Provide the full EPKINLY Prescribing Information, Adverse Reactions Management Guide, Dosing Preparation and Administration Guide, and relevant training to on-call staff. Provide EPKINLY Patient Starter Kits, which are available from your Genmab or AbbVie EPKINLY representative to new patients.
And lastly, encourage sites to prepare to support transitions of care, if applicable, as patients progress to subsequent doses.
Tara, would you like to speak further about Preparing for Adverse Reactions?
Dr. Graff: Sure. Clinics may want to prepare for the management of adverse reactions by reviewing the full Prescribing Information or the EPKINLY Adverse Reactions Management Guide.
In addition, consider the following questions.
How will you and your staff manage specific planned touchpoints, such as during calls or telehealth appointments with patients on EPKINLY during their step-up dosing in Cycle 1?
How are patients and care partners instructed to monitor for signs and symptoms of all potential adverse events, including serious adverse events?
Who should the patient or caregiver call at different times of the day, including after hours, to report symptoms of adverse reactions, or will your staff make the calls? If clinics do not have their own protocols, they can use the Patient Counseling Information in the EPKINLY Prescribing Information and the Medication Guide to develop guidance and educate patients on what to look for and when to contact the doctor.
What will your site’s protocol include to help determine a quick plan of action if a patient reports symptoms of CRS or ICANS? It’s important to advise patients to immediately contact their doctor if they experience symptoms of CRS, such as fever, shortness of breath, low blood pressure, chills, fast heartbeat, or ICANS, such as seizures, confusional state, tiredness, tremor, trouble speaking or writing, and that the onset of these symptoms may be delayed.
What patient or care partner phrases would trigger your on-call team to continue managing a patient at home versus telling them to come to the hospital or center for an evaluation?
How will the physician or advanced practice provider decide how to treat patients with symptoms of adverse events and determine if they should be admitted?
For what symptoms should the patient come to the hospital or center immediately?
What pre- and post-administration medications (such as corticosteroids like dexamethasone, diphenhydramine, or acetaminophen) will patients need before or after each EPKINLY dose?
Are appropriate agents on hand to manage CRS or ICANS if it occurs?
And which hospitals are best equipped to care for EPKINLY patients if they require hospitalization for adverse reaction management?
Clinics may also want to prepare staff by educating them about what to do for medical emergencies related to EPKINLY adverse reaction management. Please note that EPKINLY should only be administered by a qualified healthcare professional with appropriate medical support to manage severe reactions such as CRS and ICANS.
It’s important to ensure that there is an established relationship between the outpatient oncology group and hospital system to ensure prompt communication and appropriate medication and inpatient support if needed.
And lastly, ensure communication is established between all relevant providers and that the medical plan is communicated to patients and care partners.
And now let’s look at some important resources for EPKINLY. Matt?
Dr. Chui: Thanks, Tara.
Genmab and AbbVie have several resources available to help support clinics operationalizing EPKINLY.
As you can see here, there are 3 categories, and each QR code takes you to a specific resource tool.
The first one is for healthcare providers. What you will find here is information on Prescribing Information, the Video and Administration guides for dose preparation, keeping in mind the dilutions for step-up dosing. And, lastly, information regarding adverse reactions and how to manage those.
Next, we’ll move to resources for MyNavCare.com. You’ll see both the QR code and the website. And once the patients are enrolled, this is a robust program aimed to support patients on their journey with EPKINLY, keeping in mind it’s not just financial support but also social support as well.
And the last point is information regarding reimbursement and coding, and how to successfully navigate the billing cycle of EPKINLY.
Lastly, we’ll focus on the resources that are provided for patients. Some of the things you’ll find in this section are patient education tools as well as wallet cards. This information also includes educational tools for the caregiver. This website is also where you are able to print out the wallet cards that patients carry with them during EPKINLY treatment.
For additional resources, billing and coding information, and other data on EPKINLY, please reach out to your Genmab/AbbVie representative. For Medical Information questions about EPKINLY, please call 1-855-4GENMAB.
VO: INDICATIONS
DLBCL and High-grade B-cell Lymphoma
- EPKINLY is indicated for the treatment of adults 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 (HGBCL) 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 confirmatory trial(s).
Follicular Lymphoma
- EPKINLY is indicated in combination with lenalidomide and rituximab for the treatment of adults with relapsed or refractory follicular lymphoma (FL).
- EPKINLY is indicated as monotherapy for the treatment of adults with relapsed or refractory FL after 2 or more lines of systemic therapy.
IMPORTANT SAFETY INFORMATION
BOXED WARNINGS
- 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.
CRS
- CRS occurred in 51% (80/157) of patients with large B-cell lymphoma (LBCL) receiving EPKINLY at the recommended dosage schedule in EPCORE NHL-1 (37% Grade 1, 17% Grade 2, and 2.5% Grade 3) and recurred in 31% of patients. Most events (92%) occurred during Cycle 1. In Cycle 1, CRS events occurred in 6% of patients after the 0.16 mg dose (Cycle 1, day 1), 12% after the 0.8 mg dose (Cycle 1, day 8), 43% after the first 48 mg dose (Cycle 1, day 15), and 5% after the next 48 mg dose (Cycle 1, day 22). The median time to onset of CRS from the most recent administered 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 occurred in 49% (42/86) of patients with FL receiving EPKINLY monotherapy at the recommended dosage schedule in EPCORE NHL-1 (45% Grade 1, 9% Grade 2) and recurred in 48% of patients. Most events (88%) occurred during Cycle 1. In Cycle 1, CRS events occurred in 12% of patients after the 0.16 mg dose (Cycle 1, day 1), 6% after the 0.8 mg dose (Cycle 1, day 8), 15% after the 3 mg dose (Cycle 1, day 15), and 37% after the first 48 mg dose (Cycle 1, day 22). The median time to onset of CRS from the most recent administered dose across all doses was 59 hours (range: 0.1-7 days). The median time to onset after the first full 48 mg dose was 61 hours (range: 0.1-7 days).
- CRS occurred in 24% (32/131) of patients with FL receiving EPKINLY at the recommended dosage schedule in combination with lenalidomide and rituximab in EPCORE FL-1 (19% Grade 1, 5% Grade 2, and 12% serious adverse reactions due to CRS) and recurred in 41% of patients. Most events (88%) occurred during Cycle 1. In Cycle 1, CRS occurred in 5% of patients after the 0.16 mg dose (Cycle 1, day 1), 3.8% after the 0.8 mg dose (Cycle 1, day 8), 2.3% after the 3 mg dose (Cycle 1, day 15), and 18% after the first 48 mg dose (Cycle 1, day 22). The median time to onset of CRS from the most recent EPKINLY dose was 78 hours (range: 0.2-12 days). The median time to onset after the first 48 mg dose was 41 hours (range: 0.3-12 days).
- For patients with LBCL and FL, assess whether hospitalization or outpatient monitoring for the first 48 mg dose is appropriate based on comorbidities or other situational factors. During outpatient monitoring after the first 48 mg dose, patients should remain in proximity to a healthcare facility that can assess and manage CRS.
- In patients who experienced CRS, the signs and symptoms included pyrexia, hypotension, hypoxia, dyspnea, chills, and tachycardia. CRS resolved in 98% of patients; the median duration of CRS events was 2 days (range: <1-27 days). Concurrent neurological adverse reactions associated with CRS occurred in 2.5% of patients with LBCL, 4.7% of patients with FL receiving EPKINLY monotherapy, and 1.5% of patients receiving EPKINLY in combination with lenalidomide and rituximab (reactions included headache, confusional state, tremors, dizziness, and ataxia).
- Administer pretreatment medications to reduce the risk of CRS.
- Monitor patients for potential CRS. At the first signs or symptoms of CRS, immediately evaluate patients for hospitalization, manage per current practice guidelines, and administer supportive care as appropriate.
ICANS
- ICANS occurred in 6% (10/157) of patients with LBCL receiving EPKINLY at the recommended dosage schedule in EPCORE NHL-1 (4.5% Grade 1, 1.3% Grade 2, 0.6% fatal). Of the 10 ICANS events, 9 occurred within Cycle 1 of treatment, with a median time to onset of 16.5 days (range: 8-141 days) from the start of treatment. Relative to the most recent administered dose, 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.
- ICANS occurred in 6% (8/127) of patients with FL receiving EPKINLY monotherapy following the 2-step up dosage schedule in EPCORE NHL-1 (3.9% Grade 1, 2.4% Grade 2). The median time to onset was 22 days (range: 14-66 days) from the start of treatment. Relative to the most recent administered dose, the median time to onset of ICANS was 3 days (range: 0.4-7 days). The median duration of ICANS was 2 days (range: 1-7 days), with ICANS resolving in 100% of patients.
- Among patients with FL who received EPKINLY at the recommended dosage schedule in combination with lenalidomide and rituximab in EPCORE FL-1, ICANS occurred in 0.8% (1/131, Grade 1).
- The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Clinical manifestations of ICANS included, but were not limited to, confusional state, lethargy, tremor, dysgraphia, aphasia, and non-convulsive status epilepticus.
- Monitor patients for potential ICANS. At the first signs or symptoms of ICANS, immediately evaluate patient, provide supportive therapy based on severity, and manage per current practice guidelines.
Infections
- EPKINLY can cause fatal and serious infections. Serious infections, including opportunistic infections, were reported in 15% of patients with LBCL in the clinical trial (most common: 4.5% sepsis, 3.2% pneumonia). Fatal infections occurred in 1.3% of patients (1.3% COVID-19).
- Serious infections, including opportunistic infections, were reported in 40% of patients with FL receiving EPKINLY monotherapy, following the 2-step up dosage schedule in the clinical trial (most common: 20% COVID-19, 13% pneumonia, 3% urinary tract infections). Fatal infections occurred in 6% of patients (5% COVID-19, 0.8% pneumonia, 0.8% sepsis).
- Among 243 patients with FL who received EPKINLY in combination with lenalidomide and rituximab in the clinical trial, serious infections occurred in 28% of patients. The most common serious infections were pneumonia (15%), COVID-19 (7%), opportunistic infections (5%) and upper respiratory infections (3.3%). The most common opportunistic infections of any grade were CMV (cytomegalovirus) infection (7%) and herpesvirus infection (7%).
- Progressive multifocal leukoencephalopathy (PML), including fatal cases, has occurred in patients treated with EPKINLY. Across a broader clinical trial population, PML was reported in 0.4% (11/3072) of patients, including in the first-line treatment setting. Of the 11 cases of PML, 6 resulted in fatal outcomes and 1 was unresolved at the time of death.
- Monitor patients for signs and symptoms of infection and treat appropriately. Avoid administration in patients with active infections. Withhold or consider permanent discontinuation of EPKINLY based on severity. Provide Pneumocystis jirovecii pneumonia (PJP) prophylaxis during treatment with EPKINLY, and consider prophylaxis against herpesvirus.
Cytopenias
- EPKINLY can cause serious or severe cytopenias. In the clinical trial of patients with LBCL, Grade 3 or 4 decreased neutrophils occurred in 32% (Grade 4, 14%), decreased hemoglobin in 12% (Grade 4, 0%), and decreased platelets in 12% (Grade 4, 7%) of patients. Febrile neutropenia occurred in 2.5% (Grade 4, 0.6%).
- In the clinical trial of patients with FL who received EPKINLY monotherapy following the 2-step up dosage schedule, Grade 3 or 4 decreased neutrophils occurred in 30% (Grade 4, 17%), decreased hemoglobin in 10% (Grade 4, 0%), and decreased platelets in 8% (Grade 4, 4%) of patients. Febrile neutropenia occurred in 3.1% (Grade 4, 0%).
- In patients with FL who received EPKINLY in combination with lenalidomide and rituximab, Grade 3 or 4 decreased neutrophils occurred in 67% (Grade 4, 41%), decreased lymphocytes in 62% (Grade 4, 13%), decreased hemoglobin in 7%, and decreased platelets in 10% (Grade 4, 4.1%) of patients. Febrile neutropenia occurred in 6% (Grade 4, 2.1%).
- 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 when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with EPKINLY and for 4 months after the last dose. Verify pregnancy status in females of reproductive potential prior to initiating EPKINLY.
Adverse Reactions
- EPKINLY as monotherapy for LBCL or FL: Most common (≥20%) adverse reactions were CRS, injection site reactions, fatigue, musculoskeletal pain, fever, diarrhea, COVID-19, rash, and abdominal pain. Most common Grade 3 to 4 laboratory abnormalities (≥10%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, and decreased platelets.
- EPKINLY in combination with lenalidomide and rituximab for FL: Most common (≥20%) adverse reactions were 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%) were decreased neutrophils, decreased lymphocytes, and decreased platelets.
Use in Specific Populations
- Lactation: Advise women not to breastfeed during treatment and for 4 months after the last dose of EPKINLY.
- Geriatric Use: In patients with relapsed or refractory FL who received EPKINLY in EPCORE NHL-1, 52% were ≥65 years old, and 13% were ≥75 years old. A higher rate of fatal adverse reactions, primarily infections, including COVID-19, was observed in patients ≥65 years old compared to younger adult patients. No overall difference in efficacy was observed.
Please see full Prescribing Information, including Boxed Warnings.
Dr. Graff: Matt, thank you again for joining me for this program.
Dr. Chui: My pleasure.
Dr. Graff: And we thank you, our audience, for joining us.
Patient Care During Treatment
Dr. Graff: Hi everyone, and welcome to the program. I’m Dr Tara Graff, Bispecific Lead and Medical Oncologist at Mission Cancer and Blood where I also serve as Director of Clinical Trials.
The objective of this presentation is to discuss key considerations for clinics onboarding EPKINLY.
VO: SELECT IMPORTANT SAFETY INFORMATION
INDICATIONS
DLBCL and High-grade B-cell Lymphoma
- EPKINLY is indicated for the treatment of adults 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 (HGBCL) 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 confirmatory trial(s).
Follicular Lymphoma
- EPKINLY is indicated in combination with lenalidomide and rituximab for the treatment of adults with relapsed or refractory follicular lymphoma (FL).
- EPKINLY is indicated as monotherapy for the treatment of adults with relapsed or refractory FL after 2 or more lines of systemic therapy.
BOXED WARNINGS
- 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.
Please continue watching to the end of the video for additional important safety information.
Dr. Graff: Joining me for this program is Dr Matt Chui. Welcome, Matt. Please introduce yourself for our audience.
Dr. Chui: Thanks, Tara. Hi, my name is Matthew Chui. I am the Clinical Oncology Pharmacy Manager at the University of Miami Sylvester Comprehensive Cancer Center. My clinical background is in lymphoma, which has been my clinical area of expertise for the past 6 years.
Dr. Graff: It’s a pleasure to have you.
Next, let’s discuss important considerations surrounding patient care.
Clinics will want to educate patients and care partners by reviewing the care plan with them, including pre- and post-medication, step-up dosing, and overall treatment schedule, including reduction in dose frequency over time. It’s also critical to communicate information about their therapy and the need for adequate hydration prior to administration.
The clinic can consider administering pre- and post-IV fluids if there is concern the patient will not adequately hydrate at home. Share with patients and care partners the Patient Counseling Information in the Prescribing Information as well as the EPKINLY Medication Guide.
It’s important for clinics to educate patients and care partners about all potential serious adverse reactions during or after their subcutaneous injection.
Here are a few considerations:
- Highlight the signs and symptoms of adverse reactions they should call the clinician about, including CRS, neurological problems, and infections listed in the Medication Guide.
- Remind patients to monitor for symptoms of CRS, neurological problems, and infections during treatment with EPKINLY, as well as other adverse reactions, and contact the clinician if they occur.
- Encourage patients to monitor for temperature at home at least 3 times daily for 48 hours following each dose and contact the clinician if they develop a fever of 100.4 degrees or higher.
- Consider nearby lodging for patients who may live far from the treatment site.
- Discuss potential urgent care/hospital sites for management of adverse reactions.
- For patients and care partners, be sure to drive home the importance of carrying and presenting the Patient Wallet Card in the event a healthcare provider needs quick access to patient information.
- Prepare patients and their care partners prior to treatment by doing the following:
- Perform a comprehensive physical exam and routine baseline laboratory testing, including a complete blood count, or CBC, with a differential, comprehensive metabolic panel, or CMP, and a lactate dehydrogenase, or LDH prior to treatment initiation.
- Provide Pneumocystis jirovecii pneumonia (PJP) prophylaxis prior to starting treatment with EPKINLY.
And consider initiating prophylaxis against herpes virus prior to starting EPKINLY to prevent herpes zoster reactivation.
It may also be helpful to share EPKINLY patient and care partner support resources to support patient care.
Once prescribed EPKINLY, patients enrolled in MyNavCare Patient Support may receive resources and ongoing support through their treatment journey, including dedicated Patient Engagement Liaisons.
Please note that Patient Engagement Liaisons do not provide medical advice. They are trained to direct patients to speak to their healthcare provider about any treatment-related questions. Patient Engagement Liaisons can provide patients with access to helpful resources and connect patients to external organizations and support groups.
Clinics should make sure that patients and care partners have appropriate support during treatment, such as home medical services, attentive care partners, easy access to transportation, and psychological support.
For patients deemed higher-risk and for those with less social support, consider conducting a 24-hour and possibly a 48-hour post-dose phone call during step-up dosing to follow up on vital signs and inquire about symptoms.
Patients should be assessed if they need visiting nurse services and/or social work consultations for additional support.
It’s crucial that family members and other care partners have received relevant guidance. Be sure to do the following:
- Review with care partners all potential adverse events and complications, including serious adverse reactions.
- Confirm whether care partners can provide transportation to and from clinics or hospitals as needed.
- Ensure care partners have contact information for all of the patient’s healthcare providers.
In addition, review with patients and care partners what to do in case of emergency or who to call in different scenarios.
Clinics should continuously monitor and assess support that patients will receive throughout their treatment.
Next, we will focus on maintaining efficiency and communication during treatment.
Matt, I’ll turn things over to you.
Dr. Chui: Thanks, Tara.
So, there are several methods to help maintain efficiency and communication during treatment. Proactively coordinating needs for step-up, full-dose, and maintenance appointments can help maintain efficiency and communication.
It’s important to do the following:
- Order Pneumocystis jirovecii pneumonia and herpes virus prophylaxis and pre- and post-administration medications as indicated.
- Provide appropriate staffing with the most recent information on all adverse reactions that may occur in patients who are receiving EPKINLY.
- Ensure that medications are on hand to manage CRS and ICANS, if needed.
- Assess whether hospitalization or outpatient monitoring is appropriate based on comorbidities or other situational factors for the first 48 mg dose of EPKINLY for patients with either DLBCL or high-grade B-cell lymphoma on Cycle 1, Day 15, or FL on Cycle 1, Day 22.
- During outpatient monitoring after the first 48 mg dose, patients should remain in proximity to a healthcare facility that can assess and manage CRS.
- And, establish follow-up schedules with patients, including whether patients will visit the clinic multiple times throughout the week or use virtual methods for follow-ups or check-ins.
Dr. Graff: And now let’s look at some important resources for EPKINLY. Matt?
Dr. Chui: Thanks, Tara.
Genmab and AbbVie have several resources available to help support clinics operationalizing EPKINLY.
As you can see here, there are 3 categories and each QR code takes you to a specific resource tool.
The first one is for healthcare providers. What you will find here is information on Prescribing Information, the Video and Administration guides for dose preparation, keeping in mind the dilutions for step-up dosing. And, lastly, information regarding adverse reactions and how to manage those.
Next, we’ll move to resources for MyNavCare.com. You’ll see both the QR code and the website. And once the patients are enrolled, this is a robust program aimed to support patients on their journey with EPKINLY, keeping in mind It’s not just financial support but also social support as well.
And the last point is information regarding reimbursement and coding, and how to successfully navigate the billing cycle of EPKINLY.
Lastly, we’ll focus on the resources that are provided for patients. Some of the things you’ll find in this section are patient education tools as well as wallet cards. This information also includes educational tools for the caregiver. This website is also where you are able to print out the wallet cards that patients carry with them during EPKINLY treatment.
For additional resources, billing and coding information, and other data on EPKINLY, please reach out to your Genmab/AbbVie representative. For Medical Information questions about EPKINLY, please call 1-855-4GENMAB.
VO: INDICATIONS
DLBCL and High-grade B-cell Lymphoma
- EPKINLY is indicated for the treatment of adults 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 (HGBCL) 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 confirmatory trial(s).
Follicular Lymphoma
- EPKINLY is indicated in combination with lenalidomide and rituximab for the treatment of adults with relapsed or refractory follicular lymphoma (FL).
EPKINLY is indicated as monotherapy for the treatment of adults with relapsed or refractory FL after 2 or more lines of systemic therapy.
IMPORTANT SAFETY INFORMATION
BOXED WARNINGS
- 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.
CRS
- CRS occurred in 51% (80/157) of patients with large B-cell lymphoma (LBCL) receiving EPKINLY at the recommended dosage schedule in EPCORE NHL-1 (37% Grade 1, 17% Grade 2, and 2.5% Grade 3) and recurred in 31% of patients. Most events (92%) occurred during Cycle 1. In Cycle 1, CRS events occurred in 6% of patients after the 0.16 mg dose (Cycle 1, day 1), 12% after the 0.8 mg dose (Cycle 1, day 8), 43% after the first 48 mg dose (Cycle 1, day 15), and 5% after the next 48 mg dose (Cycle 1, day 22). The median time to onset of CRS from the most recent administered 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 occurred in 49% (42/86) of patients with FL receiving EPKINLY monotherapy at the recommended dosage schedule in EPCORE NHL-1 (45% Grade 1, 9% Grade 2) and recurred in 48% of patients. Most events (88%) occurred during Cycle 1. In Cycle 1, CRS events occurred in 12% of patients after the 0.16 mg dose (Cycle 1, day 1), 6% after the 0.8 mg dose (Cycle 1, day 8), 15% after the 3 mg dose (Cycle 1, day 15), and 37% after the first 48 mg dose (Cycle 1, day 22). The median time to onset of CRS from the most recent administered dose across all doses was 59 hours (range: 0.1-7 days). The median time to onset after the first full 48 mg dose was 61 hours (range: 0.1-7 days).
- CRS occurred in 24% (32/131) of patients with FL receiving EPKINLY at the recommended dosage schedule in combination with lenalidomide and rituximab in EPCORE FL-1 (19% Grade 1, 5% Grade 2, and 12% serious adverse reactions due to CRS) and recurred in 41% of patients. Most events (88%) occurred during Cycle 1. In Cycle 1, CRS occurred in 5% of patients after the 0.16 mg dose (Cycle 1, day 1), 3.8% after the 0.8 mg dose (Cycle 1, day 8), 2.3% after the 3 mg dose (Cycle 1, day 15), and 18% after the first 48 mg dose (Cycle 1, day 22). The median time to onset of CRS from the most recent EPKINLY dose was 78 hours (range: 0.2-12 days). The median time to onset after the first 48 mg dose was 41 hours (range: 0.3-12 days).
- For patients with LBCL and FL, assess whether hospitalization or outpatient monitoring for the first 48 mg dose is appropriate based on comorbidities or other situational factors. During outpatient monitoring after the first 48 mg dose, patients should remain in proximity to a healthcare facility that can assess and manage CRS.
- In patients who experienced CRS, the signs and symptoms included pyrexia, hypotension, hypoxia, dyspnea, chills, and tachycardia. CRS resolved in 98% of patients; the median duration of CRS events was 2 days (range: <1-27 days). Concurrent neurological adverse reactions associated with CRS occurred in 2.5% of patients with LBCL, 4.7% of patients with FL receiving EPKINLY monotherapy, and 1.5% of patients receiving EPKINLY in combination with lenalidomide and rituximab (reactions included headache, confusional state, tremors, dizziness, and ataxia).
- Administer pretreatment medications to reduce the risk of CRS.
- Monitor patients for potential CRS. At the first signs or symptoms of CRS, immediately evaluate patients for hospitalization, manage per current practice guidelines, and administer supportive care as appropriate.
ICANS
- ICANS occurred in 6% (10/157) of patients with LBCL receiving EPKINLY at the recommended dosage schedule in EPCORE NHL-1 (4.5% Grade 1, 1.3% Grade 2, 0.6% fatal). Of the 10 ICANS events, 9 occurred within Cycle 1 of treatment, with a median time to onset of 16.5 days (range: 8-141 days) from the start of treatment. Relative to the most recent administered dose, 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.
- ICANS occurred in 6% (8/127) of patients with FL receiving EPKINLY monotherapy following the 2-step up dosage schedule in EPCORE NHL-1 (3.9% Grade 1, 2.4% Grade 2). The median time to onset was 22 days (range: 14-66 days) from the start of treatment. Relative to the most recent administered dose, the median time to onset of ICANS was 3 days (range: 0.4-7 days). The median duration of ICANS was 2 days (range: 1-7 days), with ICANS resolving in 100% of patients.
- Among patients with FL who received EPKINLY at the recommended dosage schedule in combination with lenalidomide and rituximab in EPCORE FL-1, ICANS occurred in 0.8% (1/131, Grade 1).
- The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Clinical manifestations of ICANS included, but were not limited to, confusional state, lethargy, tremor, dysgraphia, aphasia, and non-convulsive status epilepticus.
- Monitor patients for potential ICANS. At the first signs or symptoms of ICANS, immediately evaluate patient, provide supportive therapy based on severity, and manage per current practice guidelines.
Infections
- EPKINLY can cause fatal and serious infections. Serious infections, including opportunistic infections, were reported in 15% of patients with LBCL in the clinical trial (most common: 4.5% sepsis, 3.2% pneumonia). Fatal infections occurred in 1.3% of patients (1.3% COVID-19).
- Serious infections, including opportunistic infections, were reported in 40% of patients with FL receiving EPKINLY monotherapy, following the 2-step up dosage schedule in the clinical trial (most common: 20% COVID-19, 13% pneumonia, 3% urinary tract infections). Fatal infections occurred in 6% of patients (5% COVID-19, 0.8% pneumonia, 0.8% sepsis).
- Among 243 patients with FL who received EPKINLY in combination with lenalidomide and rituximab in the clinical trial, serious infections occurred in 28% of patients. The most common serious infections were pneumonia (15%), COVID-19 (7%), opportunistic infections (5%) and upper respiratory infections (3.3%). The most common opportunistic infections of any grade were CMV (cytomegalovirus) infection (7%) and herpesvirus infection (7%).
- Progressive multifocal leukoencephalopathy (PML), including fatal cases, has occurred in patients treated with EPKINLY. Across a broader clinical trial population, PML was reported in 0.4% (11/3072) of patients, including in the first-line treatment setting. Of the 11 cases of PML, 6 resulted in fatal outcomes and 1 was unresolved at the time of death.
- Monitor patients for signs and symptoms of infection and treat appropriately. Avoid administration in patients with active infections. Withhold or consider permanent discontinuation of EPKINLY based on severity. Provide Pneumocystis jirovecii pneumonia (PJP) prophylaxis during treatment with EPKINLY, and consider prophylaxis against herpesvirus.
Cytopenias
- EPKINLY can cause serious or severe cytopenias. In the clinical trial of patients with LBCL, Grade 3 or 4 decreased neutrophils occurred in 32% (Grade 4, 14%), decreased hemoglobin in 12% (Grade 4, 0%), and decreased platelets in 12% (Grade 4, 7%) of patients. Febrile neutropenia occurred in 2.5% (Grade 4, 0.6%).
- In the clinical trial of patients with FL who received EPKINLY monotherapy following the 2-step up dosage schedule, Grade 3 or 4 decreased neutrophils occurred in 30% (Grade 4, 17%), decreased hemoglobin in 10% (Grade 4, 0%), and decreased platelets in 8% (Grade 4, 4%) of patients. Febrile neutropenia occurred in 3.1% (Grade 4, 0%).
- In patients with FL who received EPKINLY in combination with lenalidomide and rituximab, Grade 3 or 4 decreased neutrophils occurred in 67% (Grade 4, 41%), decreased lymphocytes in 62% (Grade 4, 13%), decreased hemoglobin in 7%, and decreased platelets in 10% (Grade 4, 4.1%) of patients. Febrile neutropenia occurred in 6% (Grade 4, 2.1%).
- 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 when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with EPKINLY and for 4 months after the last dose. Verify pregnancy status in females of reproductive potential prior to initiating EPKINLY.
Adverse Reactions
- EPKINLY as monotherapy for LBCL or FL: Most common (≥20%) adverse reactions were CRS, injection site reactions, fatigue, musculoskeletal pain, fever, diarrhea, COVID-19, rash, and abdominal pain. Most common Grade 3 to 4 laboratory abnormalities (≥10%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, and decreased platelets.
- EPKINLY in combination with lenalidomide and rituximab for FL: Most common (≥20%) adverse reactions were 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%) were decreased neutrophils, decreased lymphocytes, and decreased platelets.
Use in Specific Populations
- Lactation: Advise women not to breastfeed during treatment and for 4 months after the last dose of EPKINLY.
- Geriatric Use: In patients with relapsed or refractory FL who received EPKINLY in EPCORE® NHL-1, 52% were ≥65 years old, and 13% were ≥75 years old. A higher rate of fatal adverse reactions, primarily infections, including COVID-19, was observed in patients ≥65 years old compared to younger adult patients. No overall difference in efficacy was observed.
Please see full Prescribing Information, including Boxed Warnings.
Dr. Graff: Matt, thank you again for joining me for this program.
Dr. Chui: My pleasure.
Dr. Graff: And we thank you, our audience, for joining us.
Dosing & Administration
Dr. Graff: Hi everyone, and welcome to the program. I’m Dr Tara Graff, Bispecific Lead and Medical Oncologist at Mission Cancer and Blood where I also serve as Director of Clinical Trials.
The objective of this presentation is to discuss key considerations for clinics onboarding EPKINLY.
VO: SELECT IMPORTANT SAFETY INFORMATION
INDICATIONS
DLBCL and High-grade B-cell Lymphoma
- EPKINLY is indicated for the treatment of adults 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 (HGBCL) 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 confirmatory trial(s).
Follicular Lymphoma
- EPKINLY is indicated in combination with lenalidomide and rituximab for the treatment of adults with relapsed or refractory follicular lymphoma (FL).
- EPKINLY is indicated as monotherapy for the treatment of adults with relapsed or refractory FL after 2 or more lines of systemic therapy.
BOXED WARNINGS
- 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.
Please continue watching to the end of the video for additional important safety information.
Dr. Graff: Joining me for this program is Dr Matt Chui. Welcome, Matt. Please introduce yourself for our audience.
Dr. Graff: Joining me for this program is Dr Matt Chui. Welcome, Matt. Please introduce yourself for our audience.
Dr. Chui: Thanks, Tara. Hi, my name is Matthew Chui. I am the Clinical Oncology Pharmacy Manager at the University of Miami Sylvester Comprehensive Cancer Center. My clinical background is in lymphoma, which has been my clinical area of expertise for the past 6 years.
Dr. Graff: It’s a pleasure to have you.
Dr. Chui: For key considerations in the operationalization of EPKINLY, we'll move over to dosing and administration. This is both in 3L + relapse and refractory DLBCL or HGBCL as well as 2L + 3L + FL.
We'll next talk about the dosing schema, which can vary depending on the indication. The important thing to note is that EPKINLY is available off the shelf and this is given as subcutaneous therapy.
Starting on the left-hand side, the patients that have 3L + DLBCL have what’s called a 2-step up dosing schedule. This is given until patients progress or cannot tolerate it anymore. For Cycle 1, Day 1, the patients receive 0.16 mg and 0.8 mg a week later on Cycle 1, Day 8.
And then moving into Cycle 1, Day 15, that is when patients receive the first full dose at 48 mg. Then, with Cycle 1, Day 22, the patients also receive 48 mg.
And then when we talk about 3L and 2L + FL, there is by design a 3-step up dose. So, patients on Cycle 1, Day 1 and Day 8 go through their respective 0.16 and 0.8 mg doses. But then on Cycle 1, Day 15, rather than going to the first full dose of 48 mg, they actually receive a 3 mg step-up dose.
We'll see the importance of that in further slides. But on Day 22 of Cycle 1 is when these patients receive 48 mg as their first full dose.
There are some important points to consider on the bottom left-hand side. Prior to starting therapy, the patient should be on Pneumocystis jirovecii pneumonia prophylaxis as well as prophylaxis against herpes virus to prevent herpes zoster reactivation, not just for the first cycle, but throughout the entire duration of treatment.
Patients should be considered for hydration during the treatment or even prior to the treatment.
There are pre- and post-medications we'll discuss for CRS. These patients do require steroids for 3 consecutive days following each weekly administration of EPKINLY in Cycle 1. This is for each weekly therapy and if the dose of EPKINLY is delayed, you can refer to the package insert in Section 2.3 regarding how you would go about continuing or starting the step-up dosing again.
For the patients that have DLBCL for Cycles 2 and 3, these patients still require weekly treatment on Days 1, 8, 15, and 22. The dose of EPKINLY remains the same at 48 mg throughout this entire maintenance schedule.
When the patients go through Cycles 4 through 9, they de-escalate down to Days 1 and 15, so every other week of treatment. Then with Cycle 10 and beyond, the patients only receive treatment on Day 1 every 28 days. And again, as you see there, the patients are treated until they progress or cannot tolerate it due to unacceptable toxicity.
When we talk about 2L + FL in combination for Cycles 2 and 3, the patients receive a weekly treatment of EPKINLY. However, now moving down from Cycles 4 through 12, they only receive EPKINLY once every 28 days after 12 cycles of treatment. Patients would then stop therapy, making it a finite treatment.
Another important point to consider is the optionality to treat patients in the outpatient setting.
Now for 3L + DLBCL in the package insert, there is wording regarding assessing whether hospitalizing or outpatient monitoring is appropriate based on comorbidities or other situational factors.
However, it really depends on the healthcare system whether or not they want to admit those patients.
So, depending on the comfort of your health system, patients actually may be given outpatient therapy for DLBCL.
It just may depend on the institution and how stringently they monitor the patients when they come in.
Now, with the FL indication, this regimen is given in the outpatient setting by design. That's why we give the 3-mg dose on Day 15. However, patients may still have a risk for CRS and ICANS. So, you’ll want to still monitor these patients. It just depends on how you want to do that.
At this point I’ll hand things off to Tara. I know how involved you’ve been with CRS and ICANS management.
Dr. Graff: Thank you, Matt.
So, in the EPKINLY 3L + DLBCL clinical trial, safety was evaluated in 157 patients with relapsed or refractory DLBCL after 2+ lines of therapy.
CRS of any grade occurred in 51% of patients treated with EPKINLY.
In patients treated with EPKINLY, the incidence of Grade 1 CRS occurred in 37% of patients, Grade 2 CRS occurred in 17% of patients, and Grade 3 CRS occurred in 2.5% of patients. Recurrent CRS occurred in 31% of patients.
In the EPCORE® NHL-1 trial, 92% of CRS events occurred in Cycle 1 and were mostly associated with the first full 48 mg dose of EPKINLY.
The median time to onset of CRS from the most recently administered dose was 24 hours, with a range of 0 to 10 days. The median time to onset after the first full 48 mg dose was 21 hours, with a range of 0 to 7 days.
CRS resolved in 98% of patients, and the median duration of CRS events was 2 days, with a range of less than 1 to 27 days.
Management of CRS may require supportive therapy. Withhold or discontinue EPKINLY based on the severity of CRS. Please refer to the EPKINLY USPI Section 2.6.
Taking a closer look at the distribution of CRS events by dose, in Cycle 1, 6% of CRS events occurred after the 0.16 mg dose on Day 1, 12% after the 0.8 mg dose on Day 8, 43% after the 48 mg dose on Day 15, and 5% after the 48 mg dose on Day 22.
As we see here, ICANS occurred in 6% of patients who received EPKINLY.
Grade 1 incidence of ICANS occurred in 4.5% of patients, Grade 2 ICANS occurred in 1.3% of patients, and in Grade 5, 1 or 0.6% of patients it was fatal.
The median time from initiation of therapy to first ICANS onset was 16.5 days, with a range of 8 to 141 days.
The median time to onset of ICANS from the most recent administration of EPKINLY was 3 days, with a range of 1 to 13 days.
ICANS resolved in 90% of patients with supportive care, with the median time to resolution at 4 days, with a range from 0 to 8 days.
In the EPKINLY 2L + FL clinical trial, CRS occurred in 24% of patients, out of a total of 131, receiving EPKINLY at the recommended 3-step up dosage schedule.
CRS of any grade occurred in 24% of patients treated with EPKINLY. The incidence of Grade 1 CRS was 19% of patients and the incidence of Grade 2 CRS was 5%. There were no Grade 3 or Grade 4 CRS events.
Recurrent CRS occurred in 41% of patients.
Most CRS events, or 88%, occurred during Cycle 1.
The median time to onset of CRS from the most recently administered dose was 78 hours, with a range of 0.2 to 12 days. The median time to onset after the first full 48 mg dose was 41 hours, with a range of 0.3 to 12 days.
CRS resolved in 98% of patients, and the median duration of CRS events was 2 days, with a range of less than 1 to 27 days.
In the EPKINLY 3L + FL clinical trial, CRS occurred in 49% of patients, out of a total of 86, receiving EPKINLY at the recommended 3-step up dosage schedule.
CRS of any grade occurred in 49% of patients treated with EPKINLY. The incidence of Grade 1 CRS was 45% of patients and the incidence of Grade 2 CRS was 9%. There were no Grade 3 or Grade 4 CRS events.
Recurrent CRS occurred in 48% of patients.
Most CRS events, or 88%, occurred during Cycle 1.
The median time to onset of CRS from the most recently administered dose was 59 hours, with a range of 0.1 to 7 days. The median time to onset after the first full 48 mg dose was 61 hours, with a range of 0.1 to 7 days.
CRS resolved in 98% of patients, and the median duration of CRS events was 2 days, with a range of less than 1 to 27 days.
In 127 patients with FL who received EPKINLY following the 2-step up dosage schedule, ICANS events occurred in 6% of patients with FL receiving EPKINLY, utilizing the 2-step up dosage schedule; 3.9% of patients had a Grade 1 event, and 2.4% had a Grade 2 event.
The median time to onset of ICANS was 22 days from the start of treatment.
Relative to the most recent administration, the median time to onset was 3 days. ICANS resolved in 100% of patients, with the median duration of ICANS at 2 days. The median duration of exposure for patients was 8 cycles.
In 86 patients who received EPKINLY following the recommended 3-step up dosage schedule, no ICANS events were observed at the time of analysis.
The median exposure for patients in the dose optimization cohort was 5 cycles. No conclusions regarding the rate of ICANS can be made since exposure may not be sufficient in this cohort.
In 131 patients who received EPKINLY + R2 following the recommended 3-step up dosage schedule, ICANS occurred in 0.8%, or 1 out of 131 patients receiving EPKINLY with FL, with a single event reported as Grade 1.
And now let’s look at some important resources for EPKINLY, Matt?
Dr. Chui: Thanks, Tara.
Genmab and AbbVie have several resources available to help support clinics operationalizing EPKINLY.
As you can see here, there are 3 categories and each QR code takes you to a specific resource tool.
The first one is for healthcare providers. What you will find here is information on Prescribing Information, the Video and Administration guides for dose preparation, keeping in mind the dilutions for step-up dosing. And, lastly, information regarding adverse reactions and how to manage those.
Next, we’ll move to resources for MyNavCare.com. You’ll see both the QR code and the website. And once the patients are enrolled, this is a robust program aimed to support patients on their journey with EPKINLY, keeping in mind It’s not just financial support but also social support as well.
And the last point is information regarding reimbursement and coding, and how to successfully navigate the billing cycle of EPKINLY.
Lastly, we’ll focus on the resources that are provided for patients. Some of the things you’ll find in this section are patient education tools as well as wallet cards. This information also includes educational tools for the caregiver. This website is also where you are able to print out the wallet cards that patients carry with them during EPKINLY treatment.
For additional resources, billing and coding information, and other data on EPKINLY, please reach out to your Genmab/AbbVie representative. For Medical Information questions about EPKINLY, please call 1-855-4GENMAB.
VO: INDICATIONS
DLBCL and High-grade B-cell Lymphoma
- EPKINLY is indicated for the treatment of adults 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 (HGBCL) 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 confirmatory trial(s).
Follicular Lymphoma
- EPKINLY is indicated in combination with lenalidomide and rituximab for the treatment of adults with relapsed or refractory follicular lymphoma (FL).
- EPKINLY is indicated as monotherapy for the treatment of adults with relapsed or refractory FL after 2 or more lines of systemic therapy.
IMPORTANT SAFETY INFORMATION
BOXED WARNINGS
- 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.
CRS
- CRS occurred in 51% (80/157) of patients with large B-cell lymphoma (LBCL) receiving EPKINLY at the recommended dosage schedule in EPCORE NHL-1 (37% Grade 1, 17% Grade 2, and 2.5% Grade 3) and recurred in 31% of patients. Most events (92%) occurred during Cycle 1. In Cycle 1, CRS events occurred in 6% of patients after the 0.16 mg dose (Cycle 1, day 1), 12% after the 0.8 mg dose (Cycle 1, day 8), 43% after the first 48 mg dose (Cycle 1, day 15), and 5% after the next 48 mg dose (Cycle 1, day 22). The median time to onset of CRS from the most recent administered 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 occurred in 49% (42/86) of patients with FL receiving EPKINLY monotherapy at the recommended dosage schedule in EPCORE NHL-1 (45% Grade 1, 9% Grade 2) and recurred in 48% of patients. Most events (88%) occurred during Cycle 1. In Cycle 1, CRS events occurred in 12% of patients after the 0.16 mg dose (Cycle 1, day 1), 6% after the 0.8 mg dose (Cycle 1, day 8), 15% after the 3 mg dose (Cycle 1, day 15), and 37% after the first 48 mg dose (Cycle 1, day 22). The median time to onset of CRS from the most recent administered dose across all doses was 59 hours (range: 0.1-7 days). The median time to onset after the first full 48 mg dose was 61 hours (range: 0.1-7 days).
- CRS occurred in 24% (32/131) of patients with FL receiving EPKINLY at the recommended dosage schedule in combination with lenalidomide and rituximab in EPCORE FL-1 (19% Grade 1, 5% Grade 2, and 12% serious adverse reactions due to CRS) and recurred in 41% of patients. Most events (88%) occurred during Cycle 1. In Cycle 1, CRS occurred in 5% of patients after the 0.16 mg dose (Cycle 1, day 1), 3.8% after the 0.8 mg dose (Cycle 1, day 8), 2.3% after the 3 mg dose (Cycle 1, day 15), and 18% after the first 48 mg dose (Cycle 1, day 22). The median time to onset of CRS from the most recent EPKINLY dose was 78 hours (range: 0.2-12 days). The median time to onset after the first 48 mg dose was 41 hours (range: 0.3-12 days).
- For patients with LBCL and FL, assess whether hospitalization or outpatient monitoring for the first 48 mg dose is appropriate based on comorbidities or other situational factors. During outpatient monitoring after the first 48 mg dose, patients should remain in proximity to a healthcare facility that can assess and manage CRS.
- In patients who experienced CRS, the signs and symptoms included pyrexia, hypotension, hypoxia, dyspnea, chills, and tachycardia. CRS resolved in 98% of patients; the median duration of CRS events was 2 days (range: <1-27 days). Concurrent neurological adverse reactions associated with CRS occurred in 2.5% of patients with LBCL, 4.7% of patients with FL receiving EPKINLY monotherapy, and 1.5% of patients receiving EPKINLY in combination with lenalidomide and rituximab (reactions included headache, confusional state, tremors, dizziness, and ataxia).
- Administer pretreatment medications to reduce the risk of CRS.
- Monitor patients for potential CRS. At the first signs or symptoms of CRS, immediately evaluate patients for hospitalization, manage per current practice guidelines, and administer supportive care as appropriate.
ICANS
- ICANS occurred in 6% (10/157) of patients with LBCL receiving EPKINLY at the recommended dosage schedule in EPCORE NHL-1 (4.5% Grade 1, 1.3% Grade 2, 0.6% fatal). Of the 10 ICANS events, 9 occurred within Cycle 1 of treatment, with a median time to onset of 16.5 days (range: 8-141 days) from the start of treatment. Relative to the most recent administered dose, 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.
- ICANS occurred in 6% (8/127) of patients with FL receiving EPKINLY monotherapy following the 2-step up dosage schedule in EPCORE NHL-1 (3.9% Grade 1, 2.4% Grade 2). The median time to onset was 22 days (range: 14-66 days) from the start of treatment. Relative to the most recent administered dose, the median time to onset of ICANS was 3 days (range: 0.4-7 days). The median duration of ICANS was 2 days (range: 1-7 days), with ICANS resolving in 100% of patients.
- Among patients with FL who received EPKINLY at the recommended dosage schedule in combination with lenalidomide and rituximab in EPCORE FL-1, ICANS occurred in 0.8% (1/131, Grade 1).
- The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Clinical manifestations of ICANS included, but were not limited to, confusional state, lethargy, tremor, dysgraphia, aphasia, and non-convulsive status epilepticus.
- Monitor patients for potential ICANS. At the first signs or symptoms of ICANS, immediately evaluate patient, provide supportive therapy based on severity, and manage per current practice guidelines.
Infections
- EPKINLY can cause fatal and serious infections. Serious infections, including opportunistic infections, were reported in 15% of patients with LBCL in the clinical trial (most common: 4.5% sepsis, 3.2% pneumonia). Fatal infections occurred in 1.3% of patients (1.3% COVID-19).
- Serious infections, including opportunistic infections, were reported in 40% of patients with FL receiving EPKINLY monotherapy, following the 2-step up dosage schedule in the clinical trial (most common: 20% COVID-19, 13% pneumonia, 3% urinary tract infections). Fatal infections occurred in 6% of patients (5% COVID-19, 0.8% pneumonia, 0.8% sepsis).
- Among 243 patients with FL who received EPKINLY in combination with lenalidomide and rituximab in the clinical trial, serious infections occurred in 28% of patients. The most common serious infections were pneumonia (15%), COVID-19 (7%), opportunistic infections (5%) and upper respiratory infections (3.3%). The most common opportunistic infections of any grade were CMV (cytomegalovirus) infection (7%) and herpesvirus infection (7%).
- Progressive multifocal leukoencephalopathy (PML), including fatal cases, has occurred in patients treated with EPKINLY. Across a broader clinical trial population, PML was reported in 0.4% (11/3072) of patients, including in the first-line treatment setting. Of the 11 cases of PML, 6 resulted in fatal outcomes and 1 was unresolved at the time of death.
- Monitor patients for signs and symptoms of infection and treat appropriately. Avoid administration in patients with active infections. Withhold or consider permanent discontinuation of EPKINLY based on severity. Provide Pneumocystis jirovecii pneumonia (PJP) prophylaxis during treatment with EPKINLY, and consider prophylaxis against herpesvirus.
Cytopenias
- EPKINLY can cause serious or severe cytopenias. In the clinical trial of patients with LBCL, Grade 3 or 4 decreased neutrophils occurred in 32% (Grade 4, 14%), decreased hemoglobin in 12% (Grade 4, 0%), and decreased platelets in 12% (Grade 4, 7%) of patients. Febrile neutropenia occurred in 2.5% (Grade 4, 0.6%).
- In the clinical trial of patients with FL who received EPKINLY monotherapy following the 2-step up dosage schedule, Grade 3 or 4 decreased neutrophils occurred in 30% (Grade 4, 17%), decreased hemoglobin in 10% (Grade 4, 0%), and decreased platelets in 8% (Grade 4, 4%) of patients. Febrile neutropenia occurred in 3.1% (Grade 4, 0%).
- In patients with FL who received EPKINLY in combination with lenalidomide and rituximab, Grade 3 or 4 decreased neutrophils occurred in 67% (Grade 4, 41%), decreased lymphocytes in 62% (Grade 4, 13%), decreased hemoglobin in 7%, and decreased platelets in 10% (Grade 4, 4.1%) of patients. Febrile neutropenia occurred in 6% (Grade 4, 2.1%).
- 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 when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with EPKINLY and for 4 months after the last dose. Verify pregnancy status in females of reproductive potential prior to initiating EPKINLY.
Adverse Reactions
- EPKINLY as monotherapy for LBCL or FL: Most common (≥20%) adverse reactions were CRS, injection site reactions, fatigue, musculoskeletal pain, fever, diarrhea, COVID-19, rash, and abdominal pain. Most common Grade 3 to 4 laboratory abnormalities (≥10%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, and decreased platelets.
- EPKINLY in combination with lenalidomide and rituximab for FL: Most common (≥20%) adverse reactions were 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%) were decreased neutrophils, decreased lymphocytes, and decreased platelets.
Use in Specific Populations
Lactation: Advise women not to breastfeed during treatment and for 4 months after the last dose of EPKINLY.
Geriatric Use: In patients with relapsed or refractory FL who received EPKINLY in EPCORE® NHL-1, 52% were ≥65 years old, and 13% were ≥75 years old. A higher rate of fatal adverse reactions, primarily infections, including COVID-19, was observed in patients ≥65 years old compared to younger adult patients. No overall difference in efficacy was observed.
Please see full Prescribing Information, including Boxed Warnings.
Dr. Graff: Matt, thank you again for joining me for this program.
Dr. Chui: My pleasure.
Dr. Graff: And we thank you, our audience, for joining us.
2L=second line; 3L=third line; CRS=cytokine release syndrome; DLBCL=diffuse large B-cell lymphoma; FL=follicular lymphoma; ICANS=immune effector cell–associated neurotoxicity syndrome.
