Generic name: loncastuximab tesirine-lpyl
Dosage forms:  , lyophilized powder for injection, for intravenous use
Drug class: Miscellaneous antineoplastics

Medically reviewed by Melisa Puckey, BPharm. Last updated on Feb 16, 2025.

What is Zynlonta?

Zynlonta is an FDA-approved treatment for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in adults after two or more lines of systemic therapy. Relapsed cancer is cancer that comes back after past therapy has worked. Refractory cancer is when cancer treatment does not work or now no longer works. Zynlonta is a targeted therapy that binds to a protein (CD19) onto cancer cells and then releases anti-cancer medicine into the cancer cell, which dies.

Zynlonta is given as an IV infusion over 30 minutes, every three weeks.

FDA approval is for relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma. The FDA approval was granted after positive results from Zynlonta clinical trial LOTIS-2, a Phase 2 multinational, single-arm clinical trial for adult patients with r/r DLBCL. Zynlonta FDA approval was granted on April 23, 2021, for ADC Therapeutics. Zynlonta's active ingredient is loncastuximab tesirine-lpyl.

DLBCL is the most common type of non-Hodgkin lymphoma in the United States, it is a rapidly progressing, aggressive disease and often first-line treatments fail.

How Does Zynlonta Work?

Zynlonta drug class is an antibody-drug conjugate (ADC) that targets the CD19 protein.

Zynlonta mechanism of action (MOA) is the antibody section targets and binds to the CD19 protein found on the surface of B-cell lymphoma cells. Once attached the anti-cancer drug is released into cancer cells leading to cancer cell death and tumor reduction. Zynlonta targeted approach helps make treatment more effective while reducing systemic toxicity compared to traditional chemotherapy.

Zynlonta side effects

Common  Zynlonta side effects

Common side effects of Zynlonta include:

• Fatigue or weakness (38%)
• Skin rash (30%)
• Swelling - edema (28%)
• Nausea (23%)
• Muscle or joint pain (23%)
• Diarrhea (17%)
• Low appetite (15%)
• Abdominal pain (14%)
• Vomiting (13%)
• Feeling short of breath (13%)
• Constipation(12%)
• Itchy skin (12%)
• Skin photosensitivity reaction (10%)
• Fluid build up around lungs pleural effusion (10%)
• Upper respiratory tract infection (10%)
• Increased blood sugar levels
• Abnormal blood test results

These common side effects occurred in 10% or more of Zynlonta patients with R/R DLBCL in the LOTIS-2 trial.

Serious Zynlonta side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Zynlonta may cause serious side effects. Call your doctor at once if you have:

• new or worsening skin rash, peeling, redness, or irritation;
• new or worsening swelling, weight gain, chest pain, shortness of breath, or trouble breathing;
• fluid build-up in or around the lungs--pain when you breathe, feeling short of breath while lying down, wheezing, gasping for breath, cough with foamy mucus, cold and clammy skin, anxiety, rapid heartbeats;
• low blood cell counts--fever, chills, tiredness, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed or short of breath; or
• signs of a serious infection--flu symptoms, cough, weakness, body aches, headache, trouble breathing, or skin wounds with pain, redness, warmth, or swelling.

Zynlonta may also affect male fertility. Patients concerned about reproductive health should discuss their options with a healthcare provider.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Related/similar drugs

Warnings

You may get infections more easily, even serious or fatal infections. Call your doctor if you have a fever, chills, flu symptoms (cough, tiredness, weakness, body aches), headache, trouble breathing, or skin wounds with pain, redness, warmth, or swelling.

Before receiving Zynlonta

Tell your doctor if you have ever had:

• liver problems; or
• an infection.

Pregnancy 

Zynlonta can harm an unborn baby if the mother or the father is using this medicine.

• If you are a woman, you may need a pregnancy test to make sure you are not pregnant. Use birth control while using this medicine and for at least 9 months after your last dose.
• If you are a man, use birth control if your sex partner is able to get pregnant. Keep using birth control for at least 6 months after your last dose.
• Tell your doctor right away if a pregnancy occurs.

Fertility

It may be harder for a man to get a woman pregnant while using this medicine. You  should still use birth control to prevent pregnancy because the medicine can harm an unborn baby.

Breastfeeding

Do not breastfeed while using this medicine, and for at least 3 months after your last dose.

Tell your healthcare provider about all the medicines that you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get new medicine.

How do I use Zynlonta?

• Zynlonta is given to you by your healthcare provider as an intravenous (IV) infusion into your vein over 30 minutes.
• Zynlonta is usually given every 3 weeks.
• Your healthcare provider may give you medicine before each infusion to decrease your chance of side effects.
• Your healthcare provider may stop your treatment, delay your treatment, or change your dose if you have severe side effects.
• Your healthcare provider should do blood tests regularly to check for side effects.
• Your healthcare provider will decide how many treatments you need.

 Zynlonta dosing information

Usual Adult Zynlonta Dose for Lymphoma:

• 0.15 mg/kg IV over 30 minutes on Day 1 of each cycle (every 3 weeks) for 2 cycles, then 0.075 mg/kg IV over 30 minutes every 3 weeks for subsequent cycles

General dosing information

• Premedicate with dexamethasone 4 mg orally or IV 2 times a day for 3 days beginning the day before this drug.

• If dexamethasone administration does not begin the day before this drug, dexamethasone should begin at least 2 hours before administration of this drug.

Zynlonta FDA-approved use

For the treatment of adult patients with relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma.

What should I avoid while receiving Zynlonta?

Avoid or limit your exposure to sunlight, including sunlight through glass, such as buildings or vehicle windows, and artificial sunlight such as sunlamps or tanning beds. Exposure to sunlight during treatment can cause skin reactions or rash. Use sun protection measures such as sunscreen and wear loose-fitting clothes that cover your skin while out in sunlight.

Zynlonta J code

Zynlonta  J-code is J9359 (0.075 mg, injection).
J codes are used for medicines that are not taken orally and include injections, inhalations chemotherapies. J codes are important for accurate and consistent coding for billing and reimbursement purposes.

Your physician will need the Zynlonta J-code when filling out forms for your treatment.

What other drugs will affect Zynlonta?

Other drugs may interact with loncastuximab tesirine, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

Zynlonta Package Insert 

Review the Zynlonta Package Insert for more detailed information about this medicine. The Zynlonta Package Insert (PI) contains more comprehensive information on Indications and Usage, Dosage and Administration, Clinical Pharmacology, Clinical Studies, Drug Interaction, and more. Discuss any medical questions you have with your doctor or other health care provider. This is not all the information you need to know about this medicine for safe and effective use, and it does not take the place of talking to your doctor about your treatment.

The Package Insert is sometimes called the Zynlonta Prescribing Information or the FDA label.

What are the ingredients in Zynlonta?

Active ingredient: loncastuximab tesirine-lpyl
Inactive ingredients: L-histidine, L-histidine monohydrochloride, polysorbate 20, and sucrose.

Storage and Handling

• Store refrigerated at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. 
• Do not use beyond the expiration date shown on the carton.
• Do not freeze.
• Do not shake.

Special Handling

Zynlonta is a hazardous drug. Follow applicable special handling and disposal procedures.1

Any unused drug product or waste material should be disposed in accordance with local requirements.

Zynlonta manufacturer

Zynlonta manufacturer is ADC Therapeutics SA, Route de la Corniche 3B, 1066 Epalinges, Switzerland

U.S. license number 2166

Zynlonta Biosimilars

Biosimilar and interchangeable products are biological products that are highly similar to and have no clinically meaningful differences from the reference product.

Reference products

These are biological products that have already been approved by the FDA, against which biosimilar products are compared. There is 1 for Zynlonta.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer