Tepkinly (Epcoritamab)
Bispecific T-cell engager antibody for relapsed or refractory DLBCL and follicular lymphoma
Tepkinly (epcoritamab) is a bispecific T-cell engager antibody used to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) after at least two prior lines of therapy. It works by binding to both CD3 on T-cells and CD20 on B-cells, bringing immune cells into direct contact with cancer cells to trigger their destruction. Tepkinly is administered as a subcutaneous injection following a step-up dosing schedule to minimize the risk of cytokine release syndrome.
Quick Facts
Key Takeaways
- Tepkinly is a bispecific antibody that redirects your own T-cells to destroy CD20-positive lymphoma cells, used for relapsed or refractory DLBCL and follicular lymphoma after at least two prior therapies.
- Treatment follows a step-up dosing schedule starting with low priming doses (0.16 mg) and escalating to the full 48 mg dose to reduce the risk of cytokine release syndrome (CRS).
- CRS is a very common side effect, especially during early treatment cycles; pre-medications including corticosteroids, antihistamines, and acetaminophen are given before each injection.
- Serious but less common risks include ICANS (neurotoxicity), severe infections, tumor lysis syndrome, and hemophagocytic lymphohistiocytosis (HLH).
- Women of childbearing potential must use effective contraception during treatment and for at least 4 months after the last dose; breastfeeding is not recommended.
What Is Tepkinly and What Is It Used For?
Tepkinly contains the active substance epcoritamab, a bispecific antibody specifically engineered to harness the patient's own immune system to fight cancer. The drug belongs to the class of bispecific T-cell engager antibodies, a revolutionary approach in immuno-oncology that has transformed the treatment landscape for B-cell malignancies. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, epcoritamab works with precision by bringing together two key players in the immune response.
The mechanism of action involves dual binding: one arm of the antibody attaches to the CD3 receptor on T-cells (the body's primary cancer-fighting immune cells), while the other arm binds to the CD20 protein on B-cells (including malignant B-cells). By physically bridging these two cell types, epcoritamab forces the T-cells into close proximity with the cancer cells, activating the T-cells and triggering a targeted immune response that destroys the CD20-expressing tumor cells. This approach effectively redirects the patient's existing T-cell army to eliminate cancer cells that would otherwise evade immune detection.
Approved Indications
Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive non-Hodgkin lymphoma, accounting for approximately 30-40% of all newly diagnosed lymphoma cases worldwide. DLBCL can arise in lymph nodes or outside the lymphatic system (extranodal sites), and while many patients respond to first-line chemoimmunotherapy, approximately 30-40% will experience relapse or have disease that is refractory to initial treatment. For these patients, Tepkinly offers a new therapeutic option when at least two prior systemic therapies have failed.
Follicular lymphoma (FL) is a common indolent (slow-growing) non-Hodgkin lymphoma. While FL typically responds to initial therapy, it is generally considered incurable with conventional approaches, and most patients will eventually relapse. Over time, the disease may become increasingly resistant to treatment. Tepkinly provides an important alternative for FL patients who have progressed after at least two prior lines of therapy, offering a mechanism of action distinct from traditional chemoimmunotherapy regimens.
Tepkinly is used as a single-agent therapy (monotherapy), meaning it is given alone rather than in combination with other anticancer drugs. The conditional marketing authorization in the European Union reflects the promising efficacy data seen in clinical trials, with ongoing studies evaluating its long-term outcomes and potential combination strategies.
What Should You Know Before Taking Tepkinly?
Contraindications
Do not use Tepkinly if you are allergic to epcoritamab or to any of the other ingredients in this medicine (sodium acetate trihydrate, acetic acid, sorbitol, polysorbat 80, water for injections). If you are unsure whether you have any allergies to these components, speak with your doctor or nurse before receiving treatment.
Warnings and Precautions
Before starting Tepkinly, it is essential to inform your healthcare provider about your complete medical history. Certain conditions require special monitoring or may affect whether this treatment is appropriate for you. Tell your doctor, pharmacist, or nurse before receiving Tepkinly if you:
- Have or have had problems with the nervous system, such as seizures or epilepsy
- Have a current infection of any kind, whether bacterial, viral, or fungal
- Are planning to receive a vaccination or know that you may need one in the near future, as live vaccines should be avoided
Before and during treatment, your healthcare team will regularly take blood samples to monitor your antibody levels (immunoglobulin levels), assess your infection risk, and determine whether you need additional supportive treatments such as immunoglobulin replacement therapy.
- Cytokine release syndrome (CRS): A potentially life-threatening condition causing fever, vomiting, difficulty breathing, chills, rapid heartbeat, headache, and dizziness. Pre-medications are given before each injection to reduce the likelihood and severity of CRS.
- Hemophagocytic lymphohistiocytosis (HLH): A rare condition where the immune system produces excessive numbers of infection-fighting cells (histiocytes and lymfocytes), potentially leading to liver and/or spleen enlargement, heart problems, and kidney changes. Symptoms may include fever, skin rash, swollen lymph nodes, breathing difficulties, and easy bruising.
- ICANS (immune effector cell-associated neurotoxicity syndrome): Symptoms may include difficulty with speech (including speaking, understanding, writing, and reading), drowsiness, confusion/disorientation, muscle weakness, seizures, brain swelling, and memory loss.
- Infections: Signs may include fever of 38 °C or higher, chills, cough, or pain during urination; symptoms vary depending on the infection site.
- Progressive multifocal leukoencephalopathy (PML): A serious and potentially fatal brain condition with symptoms including blurred vision, vision loss, double vision, difficulty speaking, weakness or clumsiness of limbs, changes in gait or balance, personality changes, and cognitive impairment. These symptoms may begin months after treatment ends and develop gradually over weeks to months. It is important that your relatives and caregivers are also aware of these symptoms.
- Tumor lysis syndrome (TLS): Occurs when cancer cells break down rapidly, releasing their contents into the bloodstream and causing dangerous electrolyte imbalances. Your doctor will order blood tests and ensure you are well hydrated before each injection.
- Tumor flare reactions: When the cancer is being treated, it may temporarily appear to worsen before improving.
Pregnancy and Breastfeeding
Pregnancy: Tepkinly should not be used during pregnancy as it may affect the developing fetus. If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before receiving this medicine. Your doctor may require a pregnancy test before starting treatment.
Contraception: Women of childbearing potential must use effective contraception during treatment with Tepkinly and for at least 4 months after the last dose. If you become pregnant during this time, inform your doctor immediately. Discuss appropriate contraceptive methods with your healthcare provider.
Breastfeeding: Do not breastfeed during treatment with Tepkinly and for at least 4 months after the last dose. It is not known whether epcoritamab passes into breast milk or whether it could affect the nursing infant.
Fertility: The effects of Tepkinly on male and female fertility are currently unknown. Discuss fertility preservation options with your doctor before starting treatment if this is a concern.
Children and Adolescents
Tepkinly is not recommended for use in children and adolescents under 18 years of age, as there is no information on its safety or efficacy in this age group.
Driving and Operating Machinery
Due to the potential neurological side effects (ICANS), exercise caution when driving, cycling, or operating heavy or potentially dangerous machinery. If you experience neurological symptoms such as confusion, drowsiness, or difficulty with speech, avoid these activities and contact your healthcare provider immediately.
How Does Tepkinly Interact with Other Drugs?
As a bispecific antibody, epcoritamab is not metabolized by the cytochrome P450 enzyme system, which means it has a different interaction profile compared to small-molecule drugs. However, there are important clinical considerations regarding concomitant medications that patients and healthcare providers should be aware of.
Tell your doctor or pharmacist about all medications you are currently taking, have recently taken, or plan to take, including prescription drugs, over-the-counter medicines, and herbal products.
Important Drug Interactions
| Interacting Drug/Class | Type | Clinical Significance | Recommendation |
|---|---|---|---|
| Live vaccines | Contraindicated | Immunosuppression may increase risk of vaccine-related infection | Avoid live vaccines during and after treatment; use inactivated vaccines when possible |
| Antihypertensives | Clinical management | CRS-related hypotension may be exacerbated | May need temporary discontinuation during Cycle 1 |
| Immunosuppressants | Clinical management | May enhance immunosuppressive effects and infection risk | Monitor closely; discuss risk-benefit with physician |
| Anticoagulants/Antiplatelets | Monitoring advised | Tepkinly-related thrombocytopenia may increase bleeding risk | Monitor platelet counts; adjust anticoagulation as needed |
Pre-medications
Before each subcutaneous injection of Tepkinly, you will receive pre-medications to reduce the risk and severity of cytokine release syndrome (CRS) and other infusion-related reactions. These typically include:
- Corticosteroids such as dexamethasone, prednisolone, or equivalent agents
- Antihistamines such as diphenhydramine
- Acetaminophen (paracetamol) for fever prevention
During the first month of treatment (Cycle 1), adequate hydration is critical. Your doctor may instruct you to drink plenty of fluids the day before and after your injection. On the day of treatment, intravenous fluids may be administered. If you take medication for high blood pressure, your doctor may ask you to temporarily discontinue it while being treated with Tepkinly during this initial period.
What Is the Correct Dosage of Tepkinly?
Tepkinly is always administered by a physician or nurse experienced in treating cancer. It is given as a subcutaneous injection (injection under the skin) and follows a carefully designed step-up dosing schedule to minimize the risk of cytokine release syndrome. Treatment should never be self-administered.
Adults — Dosing Schedule
Tepkinly is administered in 28-day treatment cycles. The dose is gradually increased over the first cycles before reaching the full treatment dose:
| Treatment Cycle | Dosing Frequency | Dose | Notes |
|---|---|---|---|
| Cycle 1 (DLBCL) | Weekly | Day 1: 0.16 mg, Day 8: 0.8 mg, Day 15: 48 mg (full dose) | Step-up dosing to reduce CRS risk |
| Cycle 1 (FL) | Weekly | Day 1: 0.16 mg, Day 8: 0.8 mg, Day 15: 3 mg, Day 22: 48 mg | Additional intermediate dose for FL patients |
| Cycles 2–3 | Weekly (Day 1 of each cycle) | 48 mg | Full dose, continued weekly |
| Cycles 4–9 | Every 2 weeks | 48 mg | Reduced frequency as tolerated |
| Cycle 10+ | Every 4 weeks | 48 mg | Maintenance dosing; continue until progression or unacceptable toxicity |
During Cycle 1, it is critical to stay well hydrated. Your doctor may instruct you to drink plenty of water the day before and after each injection. On treatment days, intravenous fluids may be given. If you take blood pressure medication, your doctor may ask you to temporarily stop taking it during this period.
Children and Adolescents
Tepkinly is not approved for use in patients under 18 years of age. There are currently no clinical data supporting its use in pediatric populations.
Elderly Patients
No dose adjustment is required for elderly patients based on age alone. However, older patients may be at increased risk for certain adverse effects, including infections and CRS, and may require closer monitoring. Treatment decisions should be individualized based on the patient's overall health status and comorbidities.
Missed Dose
If you miss or are unable to attend your scheduled appointment, contact your healthcare provider immediately to reschedule. It is very important that you do not miss any doses, as maintaining the treatment schedule is essential for Tepkinly to be effective. Your doctor will advise you on the appropriate timing for the next dose based on when the missed dose was due.
Stopping Treatment
Do not stop treatment with Tepkinly without first discussing it with your doctor. Discontinuing treatment prematurely may allow the disease to progress. Your doctor will monitor how your treatment is working and will continue Tepkinly for as long as they believe you are benefiting from it. If necessary, your doctor may delay or permanently discontinue treatment based on the occurrence of certain side effects.
What Are the Side Effects of Tepkinly?
Like all medicines, Tepkinly can cause side effects, although not everyone experiences them. Some side effects can be serious and require immediate medical attention. The frequency and severity of side effects tend to be highest during the initial treatment cycles, particularly during the step-up dosing period, and generally decrease with subsequent cycles.
Serious Side Effects
Contact your doctor immediately if you notice any of the following serious side effects. You may experience only one or a few of these symptoms:
Very Common
- Cytokine release syndrome (CRS) — fever, vomiting, dizziness, chills, rapid heartbeat, difficulty breathing, headache
- Viral infections
- Pneumonia (lung infection)
- Upper respiratory tract infections
- Decreased appetite
- Musculoskeletal pain (bone, joint, ligament, and muscle pain)
- Abdominal pain
- Headache
- Nausea
- Diarrhea
- Skin rash
- Fatigue
- Injection site reactions
- Fever
- Edema (swelling)
- Low neutrophils (neutropenia)
- Low red blood cells (anemia)
- Low platelets (thrombocytopenia)
- Low lymphocytes (lymphopenia)
- Low immunoglobulin levels
Common
- ICANS (neurotoxicity) — difficulty speaking/writing, drowsiness, confusion, muscle weakness, seizures, memory loss
- Tumor lysis syndrome — fever, chills, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark urine, unusual fatigue, muscle/joint pain
- Febrile neutropenia (fever with low white blood cells)
- Tumor flare reactions (swollen lymph nodes, chest pain, cough, pain at tumor site)
- Fungal infections
- Skin infections
- Sepsis (life-threatening infection response)
- Irregular heart rhythm
- Pleural effusion (fluid around the lungs)
- Vomiting
- Itching (pruritus)
- Low blood phosphate, potassium, magnesium, or sodium
- Elevated blood creatinine
- Elevated liver enzymes
Uncommon
- Hemophagocytic lymphohistiocytosis (HLH) — a condition where the immune system produces excessive infection-fighting cells; symptoms include fever, skin rash, swollen lymph nodes, breathing difficulties, and easy bruising
Managing Side Effects
Your healthcare team has extensive experience in managing the side effects associated with Tepkinly. CRS is most commonly observed during the first treatment cycles and typically becomes less frequent and less severe with subsequent doses. The step-up dosing schedule is specifically designed to mitigate this risk. Pre-medications are administered before each injection, and your healthcare team will monitor you closely during and after treatment.
Regular blood tests will be performed to check for changes in your blood cell counts, electrolyte levels, kidney function, and liver function. If significant abnormalities are detected, your doctor may decide to delay treatment, adjust your dose, or provide additional supportive care such as growth factor support or blood transfusions.
Given the risk of ICANS, patients and their caregivers should be vigilant for any neurological changes, even mild ones, and report these to their healthcare team promptly. Symptoms of ICANS can appear days to weeks after injection and may initially be subtle, making early detection crucial for effective management.
How Should You Store Tepkinly?
Tepkinly is stored and handled by your doctor, nurse, or pharmacist at the hospital or clinic. Patients do not typically need to store this medication at home, as it is administered by healthcare professionals in a clinical setting. However, understanding proper storage conditions is important for ensuring the medication remains effective and safe.
- Temperature: Store and transport in a refrigerator at 2°C to 8°C (36°F to 46°F)
- Freezing: Do not freeze under any circumstances
- Light protection: Keep the vial in the outer carton to protect from light
- Expiry: Do not use after the expiration date printed on the vial label and carton (EXP). The expiration date refers to the last day of that month
- Keep out of reach: Store out of the sight and reach of children
After Dilution
The Tepkinly 4 mg/0.8 mL solution may need to be diluted before administration for the lower doses (0.16 mg and 0.8 mg). Once diluted:
- The prepared solution may be stored for up to 24 hours at 2°C to 8°C from the time of preparation
- Within these 24 hours, the solution may be kept at room temperature (20°C to 25°C) for up to 12 hours from the start of dose preparation until administration
- The solution should be brought to room temperature before injection
- No dilution is required for the 3 mg dose
Any unused medicine or waste material will be disposed of by your healthcare team in accordance with local regulations to protect the environment.
What Does Tepkinly Contain?
Active Ingredient
The active substance is epcoritamab. Each 0.8 mL vial contains 4 mg of epcoritamab at a concentration of 5 mg/mL. Epcoritamab is a humanized bispecific IgG1 antibody produced in Chinese hamster ovary (CHO) cells using recombinant DNA technology.
Inactive Ingredients (Excipients)
- Sodium acetate trihydrate — buffer to maintain pH stability
- Acetic acid — pH adjuster
- Sorbitol (E420) — stabilizer (28.8 mg per vial, equivalent to 27.33 mg/mL)
- Polysorbat 80 — surfactant to prevent protein aggregation (0.42 mg per vial, equivalent to 0.4 mg/mL). Polysorbates may cause allergic reactions; inform your doctor if you have any known allergies
- Water for injections — solvent
This medicine contains less than 1 mmol (23 mg) sodium per vial, making it essentially sodium-free. This is relevant for patients on a controlled sodium diet.
Physical Appearance
Tepkinly is a clear, colorless to slightly yellow solution for injection supplied in a single-use glass vial. Each carton contains one vial. The solution should be inspected visually before administration and must not be used if it is discolored, cloudy, or contains foreign particles.
Frequently Asked Questions About Tepkinly
Tepkinly is a bispecific T-cell engager antibody used to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) who have received at least two prior lines of systemic therapy. It works by redirecting the patient's own T-cells to attack CD20-positive cancer cells. Tepkinly is used as monotherapy (given alone, not combined with other cancer drugs).
Cytokine release syndrome (CRS) is a very common side effect of Tepkinly, affecting more than 1 in 10 patients. It occurs when activated T-cells release large amounts of inflammatory cytokines. Symptoms include fever, chills, rapid heartbeat, difficulty breathing, headache, and dizziness. CRS is most common during the early treatment cycles and is managed with pre-medications (corticosteroids, antihistamines, and acetaminophen). The step-up dosing schedule is specifically designed to reduce CRS risk.
Tepkinly is given as a subcutaneous injection (under the skin) by a healthcare professional. It follows a step-up schedule: starting with priming doses of 0.16 mg and 0.8 mg, then escalating to the full 48 mg dose. Treatment is given weekly during Cycles 1-3, every two weeks during Cycles 4-9, and every four weeks from Cycle 10 onward. Each treatment cycle is 28 days.
No. Tepkinly should not be used during pregnancy as it may harm the unborn baby. Women of childbearing potential must use effective contraception during treatment and for at least 4 months after the last dose. Breastfeeding is also not recommended during treatment and for 4 months after the final dose, as it is unknown whether epcoritamab passes into breast milk.
Tepkinly must be stored in a refrigerator at 2°C to 8°C (36°F to 46°F), protected from light in the outer carton, and must not be frozen. It is handled and stored by healthcare professionals. Once diluted, the solution can be stored for up to 24 hours refrigerated, with up to 12 hours at room temperature (20-25°C) within that window.
ICANS (immune effector cell-associated neurotoxicity syndrome) is a common side effect that affects up to 1 in 10 Tepkinly patients. It is a neurological complication that can cause difficulty speaking, writing, or reading, drowsiness, confusion, muscle weakness, seizures, and memory loss. Symptoms may appear days to weeks after injection and can be initially subtle. Patients and caregivers should report any neurological changes to their healthcare team immediately.
References
- European Medicines Agency (EMA). Tepkinly (epcoritamab) — Summary of Product Characteristics. Last updated January 2026.
- Thieblemont C, Phillips T, Ghesquieres H, et al. Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial. J Clin Oncol. 2023;41(12):2238-2247.
- Hutchings M, Mous R, Clausen MR, et al. Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 trial. Lancet. 2021;398(10306):1157-1169.
- National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: B-Cell Lymphomas. Version 2.2026.
- Morschhauser F, Kazantsev N, Middeke JM, et al. Epcoritamab in relapsed/refractory follicular lymphoma: results from the EPCORE NHL-2 trial. Blood. 2024;143(24):2501-2511.
- European Society for Medical Oncology (ESMO). Clinical Practice Guidelines: Diffuse Large B-Cell Lymphoma. 2024 Update.
- World Health Organization (WHO). WHO Model List of Essential Medicines. 23rd edition, 2023.
- Lee DW, Santomasso BD, Locke FL, et al. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019;25(4):625-638.
Editorial Team
Written by the iMedic Medical Editorial Team, specialists in oncology, hematology, and clinical pharmacology.
Reviewed by the iMedic Medical Review Board following EMA, FDA, and NCCN guidelines. GRADE evidence framework applied.
Published: | Last reviewed: | Evidence level: 1A — Based on approved product labeling, randomized controlled trials, and international clinical practice guidelines.