Zynlonta: Uses, Dosage & Side Effects
A CD19-directed antibody-drug conjugate (ADC) for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy
Zynlonta (loncastuximab tesirine) is an antibody-drug conjugate (ADC) used to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received two or more prior lines of systemic therapy. It consists of a humanized monoclonal antibody targeting the CD19 protein on B-cells, linked to a potent pyrrolobenzodiazepine (PBD) dimer cytotoxin that kills cancer cells by creating irreversible crosslinks in their DNA. Zynlonta is administered as an intravenous infusion every three weeks in a hospital or clinic setting and requires a prescription. It has been granted conditional marketing authorization in the EU and accelerated approval in the US, providing an important treatment option for patients with this difficult-to-treat cancer.
Quick Facts: Zynlonta
Key Takeaways
- Zynlonta (loncastuximab tesirine) is a CD19-directed antibody-drug conjugate that delivers a potent DNA-crosslinking payload directly to B-cell cancer cells, providing a targeted treatment option for relapsed or refractory DLBCL after two or more prior therapies.
- Treatment is given as a 30-minute intravenous infusion every 3 weeks, with a higher dose (0.15 mg/kg) for the first two cycles and a reduced maintenance dose (0.075 mg/kg) from cycle 3 onwards, always preceded by dexamethasone premedication.
- Key safety concerns include fluid retention (edema, pleural and pericardial effusions), myelosuppression (low blood counts), serious infections, and photosensitivity reactions – patients must use sunscreen and protective clothing throughout treatment.
- Zynlonta must not be used during pregnancy; women of childbearing potential must use effective contraception during treatment and for 10 months after the last dose, and men for 7 months after the last dose.
- The LOTIS-2 clinical trial demonstrated an overall response rate of approximately 48% in heavily pretreated DLBCL patients, with a complete response rate of approximately 24%, establishing Zynlonta as a meaningful option in the relapsed/refractory setting.
What Is Zynlonta and What Is It Used For?
Zynlonta contains the active substance loncastuximab tesirine, an innovative type of anticancer medication classified as an antibody-drug conjugate (ADC). ADC technology combines the specificity of a monoclonal antibody with the potent cell-killing ability of a cytotoxic drug, enabling targeted delivery of the toxic payload directly to cancer cells while limiting damage to healthy tissue. In the case of Zynlonta, the antibody component is a humanized immunoglobulin G1 (IgG1) monoclonal antibody engineered to recognize and bind to CD19, a transmembrane protein that is broadly expressed on the surface of B-lymphocytes throughout their development from pro-B cells to mature B-cells, including malignant B-cells found in various lymphomas.
The cytotoxic payload of Zynlonta is a pyrrolobenzodiazepine (PBD) dimer known as SG3199. This PBD dimer is connected to the antibody via a cathepsin B-cleavable valine-alanine peptide linker. Once the antibody binds to CD19 on the surface of a B-cell, the entire ADC complex is internalized into the cell via receptor-mediated endocytosis. Within the lysosomes of the cell, the linker is cleaved by cathepsin B enzymes, releasing the SG3199 payload. The released PBD dimer binds in the minor groove of DNA and forms covalent interstrand crosslinks between the two strands of the DNA double helix. These crosslinks are irreversible and prevent the DNA strands from separating, which is essential for DNA replication and transcription. As a result, the cancer cell cannot divide and undergoes apoptotic cell death. Because PBD dimers do not distort the DNA helix upon binding, they may evade some DNA repair mechanisms, making them particularly potent cytotoxic agents.
CD19 is an attractive therapeutic target for B-cell malignancies because it is expressed on the vast majority of B-cell lymphomas, including DLBCL. Unlike some other surface markers, CD19 is present on cancer cells even after they have acquired resistance to prior therapies, which makes it a reliable target for heavily pretreated patients. CD19 expression on normal cells is largely restricted to the B-cell lineage, which helps limit off-target toxicity compared with less selective chemotherapy approaches.
Zynlonta is approved for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received two or more prior lines of systemic therapy. DLBCL is the most common type of non-Hodgkin lymphoma worldwide, accounting for approximately 30–40% of all newly diagnosed non-Hodgkin lymphomas. It is an aggressive (fast-growing) cancer that develops from B-lymphocytes. While many patients with DLBCL are cured with first-line chemoimmunotherapy (typically R-CHOP: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), a significant proportion – approximately 30–40% – will experience relapsed or refractory disease. For these patients, treatment options become increasingly limited with each subsequent line of therapy, and prognosis worsens considerably. Zynlonta addresses this important unmet medical need.
The approval of Zynlonta was primarily based on the results of the LOTIS-2 clinical trial (NCT03589469), an open-label, single-arm, multicenter Phase 2 study. LOTIS-2 enrolled 145 patients with relapsed or refractory DLBCL who had received at least two prior lines of therapy. The study demonstrated an overall response rate (ORR) of 48.3%, with 24.1% of patients achieving a complete response (CR) and 24.1% achieving a partial response. The median duration of response was 10.3 months, and responses were observed across patient subgroups regardless of prior CAR-T cell therapy, number of prior treatment lines, or disease biology. These results were considered clinically meaningful in a patient population with very limited remaining treatment options.
Unlike many conventional chemotherapy drugs, the PBD dimer payload of Zynlonta does not distort the DNA helix when it forms crosslinks. This means the DNA damage may be less readily detected by the cell’s repair machinery, potentially making the drug effective even in cancer cells that have developed resistance to other DNA-damaging agents. This unique mechanism of action contributes to Zynlonta’s activity in heavily pretreated patients.
What Should You Know Before Receiving Zynlonta?
Contraindications
Zynlonta is contraindicated in patients with a known hypersensitivity to loncastuximab tesirine or to any of the excipients in the formulation (L-histidine, L-histidine monohydrochloride, polysorbate 20, and sucrose). If you have experienced a severe allergic reaction to any of these components in the past, you should not receive Zynlonta. There are no other absolute contraindications listed in the prescribing information, but several important warnings and precautions must be considered before starting treatment.
Warnings and Precautions
Before and during treatment with Zynlonta, your doctor will carefully assess your medical condition and monitor you for potential complications. Inform your healthcare team immediately if you experience any of the following:
Serious infections, including life-threatening infections, have occurred in patients treated with Zynlonta. Tell your doctor or nurse immediately if you develop new or worsening signs of infection, such as fever, chills, flu-like symptoms (cough, fatigue, weakness, body aches), severe headache, or wounds that appear red, warm, swollen, or painful. Your doctor may need to delay, reduce, or discontinue treatment.
Your body may retain excess fluid during treatment with Zynlonta. This can be serious and may manifest as swelling in the hands, feet, face, legs, or joints (edema), shortness of breath (which may indicate fluid around the lungs – pleural effusion), or chest pain (which may indicate fluid around the heart – pericardial effusion). Tell your doctor or nurse immediately if you notice sudden weight gain, new or worsening swelling, or difficulty breathing. In severe cases, your doctor may need to pause treatment until the fluid retention resolves. A condition called capillary leak syndrome, where blood leaks from small blood vessels into the body, has also been reported.
Zynlonta commonly causes decreases in platelets (thrombocytopenia), white blood cells (neutropenia), and red blood cells (anemia). Your doctor will perform regular blood tests to monitor your blood counts throughout treatment. Low blood counts can increase your risk of bleeding, infection, and fatigue. Tell your doctor immediately if you notice unusual bruising or bleeding, signs of infection, or excessive tiredness.
Serious skin reactions have occurred in patients treated with Zynlonta. Exposure to sunlight – including through glass or car windows – can cause severe sunburn-like reactions, including skin peeling and irritation. You must use broad-spectrum sunscreen (SPF 30 or higher), wear protective clothing (long sleeves, hats, sunglasses), and avoid prolonged exposure to sunlight during and after treatment. Itchy rashes, blistering, darker skin patches, and reactions at the injection site have also been reported. Tell your doctor or nurse immediately if you develop any new or worsening skin changes.
- Active infections: If you have an active infection or have recently had one, tell your doctor before starting treatment. Your infection may need to be treated or resolved before Zynlonta can be given safely.
- Liver problems: If you have or have had liver disease, inform your doctor. Symptoms of liver problems may include yellowing of the skin or eyes (jaundice). Your doctor will monitor liver function tests during treatment.
- Kidney problems: Although no specific dose adjustments are required for mild to moderate kidney impairment, inform your doctor about any kidney conditions.
Pregnancy, Breastfeeding, and Fertility
Zynlonta can harm an unborn child and should not be used during pregnancy. Based on its mechanism of action and preclinical data, the PBD dimer cytotoxin component is expected to be genotoxic and teratogenic. Before starting treatment, your doctor may ask you to take a pregnancy test to confirm you are not pregnant.
Contraception: Women of childbearing potential must use effective contraception during treatment with Zynlonta and for at least 10 months after the last dose. Men with partners who could become pregnant must use effective contraception during treatment and for at least 7 months after the last dose. Discuss contraceptive options with your doctor.
Breastfeeding: You should not breastfeed during treatment with Zynlonta and for at least 3 months after the last dose. It is unknown whether Zynlonta or its metabolites pass into breast milk, but a risk to the breastfed infant cannot be excluded.
Fertility: Zynlonta may impair male fertility. Men should consider having sperm samples cryopreserved (frozen) before starting treatment. Consult your doctor for more information about fertility preservation options.
Driving and Operating Machinery
Zynlonta has no or negligible direct effect on the ability to drive or use machines. However, if you experience infusion-related reactions, fatigue, weakness, or dizziness (see side effects), you should not drive, cycle, or use tools or machinery until you feel better.
Important Information About Ingredients
Each vial of Zynlonta contains polysorbate 20 (0.4 mg per vial, corresponding to 0.2 mg/mL after reconstitution). Polysorbates can cause allergic reactions in some individuals. If you have any known allergies to polysorbate or similar surfactants, inform your doctor before treatment.
How Does Zynlonta Interact with Other Drugs?
Drug interactions with Zynlonta primarily involve the cytotoxic PBD dimer payload SG3199, which is released intracellularly after the antibody binds to CD19 on cancer cells. SG3199 and its metabolite SG2057 are metabolized by cytochrome P450 enzymes, primarily CYP3A4 and CYP2C8. Medications that inhibit or induce these enzymes could theoretically alter the exposure to the cytotoxic payload and its metabolites. However, because the PBD dimer is released primarily within target cells rather than systemically, the clinical significance of these interactions may differ from conventional small molecule drugs. It is essential to inform your doctor about all medications, supplements, and herbal products you are taking.
Major Interactions
| Interacting Drug | Effect | Clinical Significance |
|---|---|---|
| Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin) | May increase SG3199/SG2057 exposure, potentially increasing toxicity | Use with caution; monitor closely for increased side effects |
| Strong CYP3A4 inducers (e.g., rifampicin, carbamazepine, phenytoin) | May decrease SG3199 exposure, potentially reducing efficacy | Avoid combination if possible; efficacy may be diminished |
| Live vaccines (e.g., MMR, varicella, BCG, yellow fever) | Risk of vaccine-strain infection due to immunosuppression | Avoid during and after treatment until immune recovery |
| Other immunosuppressive agents | Additive immunosuppression, increased infection risk | Monitor closely for infections; consider prophylaxis |
Minor Interactions
| Interacting Drug | Effect | Clinical Significance |
|---|---|---|
| CYP2C8 inhibitors (e.g., gemfibrozil, trimethoprim) | May modestly increase SG2057 metabolite levels | Use with caution; clinical significance uncertain |
| Moderate CYP3A4 inhibitors (e.g., erythromycin, fluconazole, grapefruit juice) | Possible modest increase in PBD dimer exposure | Use with caution; monitor for increased side effects |
| Dexamethasone (co-administered as premedication) | Required co-administration to reduce side effects; may also have anti-lymphoma activity | Mandatory premedication – not an adverse interaction |
| Inactivated vaccines | Reduced immune response to vaccination | Vaccination may be less effective; discuss timing with your doctor |
Because Zynlonta causes B-cell depletion (CD19 is expressed on all B-cells, not just cancer cells), patients may have reduced antibody production and impaired immune responses for a period during and after treatment. This should be considered when planning vaccinations or when there is a risk of exposure to infectious diseases. Your oncologist will take all of your medications into account when planning your treatment regimen.
What Is the Correct Dosage of Zynlonta?
Zynlonta is always administered by a doctor or nurse as an intravenous infusion over 30 minutes under medical supervision. The dose is calculated individually based on your body weight. Your doctor will determine the duration of treatment based on your response and tolerability.
Dosing Schedule
| Treatment Cycle | Dose | Frequency |
|---|---|---|
| Cycle 1 | 0.15 mg/kg | Day 1 of a 21-day cycle |
| Cycle 2 | 0.15 mg/kg | Day 1 of a 21-day cycle |
| Cycle 3 and beyond | 0.075 mg/kg | Day 1 of a 21-day cycle |
Dexamethasone Premedication
Required Premedication with Dexamethasone
Standard regimen: Dexamethasone 4 mg is given orally or intravenously twice daily for 3 days, beginning the day before each Zynlonta infusion.
If not given the day before: If you did not receive dexamethasone the day before your scheduled treatment, it must be given at least 2 hours before the Zynlonta infusion.
Purpose: Dexamethasone premedication helps reduce the risk and severity of certain side effects, including edema and effusions.
Dose Adjustments
Your doctor may need to adjust your dose, delay treatment, or discontinue Zynlonta in the following situations:
- Myelosuppression: If your blood cell counts drop to critically low levels (severe neutropenia, thrombocytopenia, or anemia), treatment may be delayed until counts recover sufficiently. Dose reduction may be considered for recurrent myelosuppression.
- Fluid retention: If you develop severe edema or effusions, treatment may be withheld until the fluid retention has resolved. Your doctor will provide appropriate supportive treatment.
- Skin reactions: If you develop severe skin reactions, treatment may be delayed or discontinued depending on severity.
- Infections: If you develop a serious infection, treatment will be withheld until the infection is adequately controlled.
- Liver toxicity: If liver enzyme elevations become significant, dose modifications may be necessary.
Children
Zynlonta is intended for use in adult patients only. The safety and efficacy of loncastuximab tesirine in children and adolescents below 18 years of age have not been established. There is no data available for use in this population, and Zynlonta should not be administered to pediatric patients.
Missed Dose
If you miss a scheduled dose of Zynlonta, you should receive it as soon as possible. Your doctor may need to reschedule your next planned dose to maintain the 21-day interval between doses. Do not try to “catch up” by receiving a double dose. Contact your healthcare team to arrange a new appointment.
Overdose
Since Zynlonta is administered by healthcare professionals in a clinical setting, overdose is unlikely. However, if an overdose were to occur, your doctor would monitor you closely and provide supportive treatment as needed. There is no specific antidote for loncastuximab tesirine.
How Zynlonta Is Prepared and Given
Zynlonta is supplied as a white to off-white lyophilized (freeze-dried) powder with a cake-like appearance in a single-use glass vial containing 10 mg of loncastuximab tesirine. Before administration, the powder must be reconstituted with 2.2 mL of sterile water for injection to achieve a concentration of 5 mg/mL. The reconstituted solution should be clear to slightly opalescent and colorless to slightly yellow. The required dose volume is then withdrawn and added to a 50 mL infusion bag containing 5% glucose (dextrose) solution for intravenous administration.
The prepared infusion is given intravenously over 30 minutes through a dedicated infusion line equipped with a sterile, non-pyrogenic, low protein-binding in-line or add-on filter (0.2 or 0.22 micrometer pore size). Zynlonta must not be given as an intravenous push or bolus injection, and it must not be mixed with other medications. The reconstituted solution should be used within 4 hours if kept at room temperature or refrigerated, and the diluted infusion solution should be used within 24 hours if refrigerated or within 8 hours at room temperature.
Zynlonta is always prepared and administered by trained healthcare professionals experienced in the use of anticancer therapies, in a hospital or specialized clinic setting. You will not self-administer this medication at home. Each infusion is carefully calculated based on your body weight and clinical condition. Zynlonta is a cytotoxic drug and must be handled according to applicable safety procedures.
What Are the Side Effects of Zynlonta?
Like all medicines, Zynlonta can cause side effects, although not everyone experiences them. The following side effects have been reported in clinical trials and post-marketing experience. Your medical team will monitor you closely and manage side effects as they arise. It is important to report any new symptoms to your doctor or nurse promptly.
Serious Side Effects
The following serious side effects require immediate medical attention. Tell your doctor or nurse right away if you experience any of these:
- Infections: Serious and life-threatening infections, including pneumonia, sepsis, and opportunistic infections, have occurred. Signs include fever, chills, cough, fatigue, weakness, body aches, severe headache, or wounds that appear red, warm, swollen, or painful.
- Fluid retention: Edema (swelling in hands, feet, face, legs), pleural effusion (fluid around the lungs causing shortness of breath), pericardial effusion (fluid around the heart causing chest pain), and ascites (fluid in the abdomen) can occur. Capillary leak syndrome has also been reported.
- Myelosuppression: Severe decreases in blood cell counts can lead to bleeding (from low platelets), infections (from low white blood cells), and severe fatigue (from low red blood cells).
- Skin reactions: Severe photosensitivity reactions resembling sunburn, skin peeling, blistering, and irritation at the injection site.
Side Effects by Frequency
Very Common
May affect more than 1 in 10 people
- Thrombocytopenia (low platelet count)
- Neutropenia (low white blood cell count)
- Anemia (low red blood cell count)
- Fatigue and pale skin
- Elevated liver enzymes (gamma-GT, AST, ALT)
- Edema (swelling in hands, feet, face, or legs)
- Pleural effusion (fluid around the lungs)
- Shortness of breath (dyspnea)
- Decreased appetite
- Nausea or vomiting
- Diarrhea
- Abdominal pain
- Constipation
- Skin redness (erythema)
- Skin rash
- Itching (pruritus)
Common
May affect up to 1 in 10 people
- Lung infections including bronchitis or pneumonia
- Sepsis (life-threatening infection throughout the body)
- Upper respiratory tract infection (cold or sore throat)
- Pericardial effusion (fluid around the heart)
- Ascites (fluid in the abdomen)
- Chest pain
- Maculopapular rash (flat, red area covered with small raised bumps)
- Photosensitivity (sensitivity to sunlight)
- Muscle pain (myalgia)
- Joint pain (arthralgia)
- Back and neck pain
- Pain in arms and legs
- Lack of energy
Uncommon
May affect up to 1 in 100 people
- Pustular rash (pus-filled raised bumps on skin)
- Discomfort in arms and legs
- Musculoskeletal discomfort
- Pericarditis (inflammation of the membrane around the heart)
Not Known
Frequency cannot be estimated from available data
- Spider veins (broken blood vessels near the skin surface)
- Skin blisters
- Vesicular rash (small fluid-filled blisters)
- Cutaneous collagen vasculopathy (small red or purple spots starting on the legs, usually painless)
Photosensitivity Advisory
Photosensitivity is an important and characteristic side effect of Zynlonta that deserves special attention. The PBD dimer payload can make your skin abnormally sensitive to ultraviolet (UV) light. This means that even brief exposure to sunlight – including through glass or car windows – can cause severe reactions resembling sunburn. These reactions may include skin redness, peeling, irritation, pain, and blistering. To protect yourself:
- Apply broad-spectrum sunscreen (SPF 30 or higher) to all exposed skin every day, even on cloudy days
- Wear protective clothing: long sleeves, long pants, wide-brimmed hats, and UV-protective sunglasses
- Avoid direct sunlight during peak UV hours (typically 10 AM to 4 PM)
- Be aware that UV light can penetrate windows, so take precautions even when indoors near windows or in cars
- Report any skin changes to your healthcare team promptly
It is important to report suspected side effects after a medicine has been authorized. This allows continuous monitoring of the benefit-risk balance of the medicine. Healthcare professionals and patients are encouraged to report any suspected adverse reactions to their national pharmacovigilance agency (e.g., FDA MedWatch in the US, Yellow Card Scheme in the UK, or the relevant national authority in your country).
How Should Zynlonta Be Stored?
Zynlonta will be stored by the doctors, pharmacists, and nurses at the hospital or clinic where you receive treatment. You do not need to store this medicine at home. The following storage information is provided for completeness:
- Unopened vials: Store in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze. Keep the vial in the outer carton to protect from light.
- Reconstituted solution: Should be used immediately. If not used right away, it may be stored for up to 4 hours in the refrigerator (2–8°C) or up to 4 hours at room temperature (20–25°C), provided reconstitution was performed under appropriate aseptic conditions.
- Diluted infusion solution: Should be used immediately. If not used right away, it may be stored for up to 24 hours in the refrigerator (2–8°C) or up to 8 hours at room temperature (20–25°C), provided dilution was performed under appropriate aseptic conditions.
- Do not expose the reconstituted or diluted solution to direct sunlight or freeze it.
- Do not use this medicine after the expiry date stated on the carton and vial label (EXP). The expiry date refers to the last day of that month.
- Keep out of sight and reach of children.
Zynlonta is a cytotoxic medication. Applicable handling and disposal procedures for anticancer drugs must be followed. Healthcare professionals are responsible for the proper disposal of any unused Zynlonta in accordance with local regulations to protect the environment.
What Does Zynlonta Contain?
Zynlonta is supplied as a sterile, preservative-free, white to off-white lyophilized (freeze-dried) powder with a cake-like appearance. It is provided in a single-use glass vial.
Active Ingredient
The active substance is loncastuximab tesirine. Each vial contains 10 mg of loncastuximab tesirine. After reconstitution with 2.2 mL of sterile water for injection, each mL of the reconstituted solution contains 5 mg of loncastuximab tesirine. Loncastuximab tesirine is an antibody-drug conjugate consisting of a humanized anti-CD19 IgG1 monoclonal antibody covalently linked to a pyrrolobenzodiazepine (PBD) dimer cytotoxin (SG3199) through a cathepsin B-cleavable valine-alanine linker with an average drug-to-antibody ratio (DAR) of approximately 2.3.
Inactive Ingredients (Excipients)
| Excipient | Function |
|---|---|
| L-Histidine | Buffer (maintains pH stability) |
| L-Histidine monohydrochloride | Buffer (maintains pH stability) |
| Polysorbate 20 (E432) | Surfactant (stabilizer to prevent aggregation) |
| Sucrose | Cryoprotectant and tonicity agent |
Each carton contains one single-use vial. The powder must be reconstituted and diluted before intravenous infusion. The reconstituted solution should be inspected for particulate matter and discoloration before use. Do not use if the solution is discolored, cloudy, or contains visible particles.
Zynlonta has been granted conditional marketing authorization in the EU. This means that further data on the medicine are expected. The European Medicines Agency reviews new information about Zynlonta at least annually and updates the product information as needed. In the US, Zynlonta received accelerated approval from the FDA based on the LOTIS-2 trial results, with confirmatory studies ongoing.
Frequently Asked Questions About Zynlonta
Zynlonta is specifically approved for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in adults who have received at least two prior lines of systemic therapy. DLBCL is the most common type of aggressive non-Hodgkin lymphoma, accounting for about 30–40% of newly diagnosed non-Hodgkin lymphoma cases worldwide. By targeting CD19 on B-cells, Zynlonta provides a treatment option for patients whose cancer has returned or not responded to previous therapies.
In the LOTIS-2 clinical trial, Zynlonta demonstrated an overall response rate of approximately 48% in patients with relapsed or refractory DLBCL who had received at least two prior therapies. About 24% of patients achieved a complete response (complete disappearance of detectable cancer), and the median duration of response was 10.3 months. These results are considered clinically meaningful in a heavily pretreated patient population with very limited alternative treatment options.
Dexamethasone is given as mandatory premedication before each Zynlonta infusion to help reduce the risk and severity of certain side effects, particularly fluid retention (edema and effusions). The standard regimen is dexamethasone 4 mg orally or intravenously twice daily for 3 days, starting the day before the Zynlonta infusion. If not given the day before, dexamethasone must be administered at least 2 hours before the infusion. Dexamethasone is a corticosteroid with anti-inflammatory properties and may also have some direct anti-lymphoma activity.
Yes, Zynlonta has shown activity in patients who have previously received CAR-T cell therapy. In the LOTIS-2 trial, a subset of patients had received prior CAR-T cell therapy, and responses were observed in this subgroup as well. Because Zynlonta targets CD19 (the same antigen targeted by many CAR-T products), there were initial questions about whether CD19 loss after CAR-T might limit efficacy, but clinical data suggest that Zynlonta remains effective in many of these patients. Your doctor will consider your prior treatment history when deciding if Zynlonta is appropriate.
The duration of treatment with Zynlonta varies depending on how well you respond and how well you tolerate the drug. Treatment typically continues until disease progression or unacceptable toxicity. Each treatment cycle is 21 days, and you receive one infusion per cycle. In the LOTIS-2 trial, patients received a median of approximately 4–5 cycles. Even if your symptoms improve, you should continue treatment until your doctor determines it is appropriate to stop, as discontinuing too early may allow the cancer to return.
All information is based on international medical guidelines and peer-reviewed research: the EMA Summary of Product Characteristics for Zynlonta, FDA prescribing information, the LOTIS-2 clinical trial published in The Lancet Oncology, NCCN Clinical Practice Guidelines for B-Cell Lymphomas (2025), and ESMO Clinical Practice Guidelines for diffuse large B-cell lymphoma. All medical claims reflect the most current evidence available and are reviewed according to the GRADE evidence framework.
References
- European Medicines Agency (EMA). Zynlonta (loncastuximab tesirine) – Summary of Product Characteristics. Last updated 2026. Available at: EMA – Zynlonta
- U.S. Food and Drug Administration (FDA). Zynlonta (loncastuximab tesirine-lpyl) – Prescribing Information. Approved April 2021, updated 2024. Available at: FDA Drugs@FDA.
- Caimi PF, Ai W, Alderuccio JP, et al. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. The Lancet Oncology. 2021;22(6):790–800. doi:10.1016/S1470-2045(21)00139-X
- National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: B-Cell Lymphomas. Version 2.2025. Available at: nccn.org.
- European Society for Medical Oncology (ESMO). Clinical Practice Guidelines: Diffuse Large B-Cell Lymphoma. Updated 2024. Available at: esmo.org.
- Tilly H, Morschhauser F, Sehn LH, et al. Polatuzumab vedotin in previously untreated diffuse large B-cell lymphoma. New England Journal of Medicine. 2022;386(4):351–363. doi:10.1056/NEJMoa2115304
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List. 2023. Available at: who.int.
- Hamadani M, Radford J, Carlo-Stella C, et al. Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma. Blood. 2021;137(19):2634–2645. doi:10.1182/blood.2020007512
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