Zynlonta

ZYNLONTA is indicated for the treatment of adult patients with relapsed or refractory 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.

This indication is approved under accelerated approval based on overall response rate

• ZYNLONTA is an intravenous infusion over 30 minutes on Day 1 of each cycle (every 3 weeks). The recommended dosage is:
  • 0.15 mg/kg every 3 weeks for 2 cycles.
  • 0.075 mg/kg every 3 weeks for subsequent cycles. (
    2.1 Recommended Dosage

    ZYNLONTA as an intravenous infusion administered over 30 minutes on Day 1 of each cycle (every 3 weeks). Administer intravenous infusion as follows:

    • 0.15 mg/kg every 3 weeks for 2 cycles.
    • 0.075 mg/kg every 3 weeks for subsequent cycles.
    )
• Premedicate with dexamethasone 4 mg orally or intravenously twice daily for 3 days beginning the day before ZYNLONTA. (
  2.2 Recommended Premedication

  Unless contraindicated, administer dexamethasone 4 mg orally or intravenously twice daily for 3 days beginning the day before administering ZYNLONTA. If dexamethasone administration does not begin the day before ZYNLONTA, dexamethasone should begin at least 2 hours prior to administration of ZYNLONTA.
  )
• See Full Prescribing Information for instructions on preparation and administration. (
  2.4 Reconstitution and Administration Instructions

  Reconstitute and further dilute ZYNLONTA prior to intravenous infusion. Use appropriate aseptic technique.

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

  Dose calculation

  Calculate the total dose (mg) required based on the patient's weight and prescribed dose

  [see Dosage and Administration (2.1)]

  .

  • For patients with a body mass index (BMI) ≥35 kg/m², calculate the dose based on an adjusted body weight (ABW) as follows:
    
    ABW in kg = 35 kg/m²× (height in meters)²
  • More than one vial may be needed to achieve the calculated dose.
  • Convert the calculated dose (mg) to volume using 5 mg/mL, which is the concentration of ZYNLONTA after reconstitution.

  Reconstitution of lyophilized ZYNLONTA

  • Reconstitute each ZYNLONTA vial using 2.2 mL of Sterile Water for Injection, USP with the stream directed toward the inside wall of the vial to obtain a final concentration of 5 mg/mL.
  • Swirl the vial gently until the powder is completely dissolved.
    Do not shake
    .
    Do not expose to direct sunlight.
  • Inspect the reconstituted solution for particulate matter and discoloration. The solution should appear clear to slightly opalescent, colorless to slightly yellow. Do not use if the reconstituted solution is discolored, is cloudy, or contains visible particulates.
  • Use reconstituted ZYNLONTA immediately. If not used immediately, store the reconstituted solution in the vial for up to 4 hours refrigerated at 2°C to 8°C (36°F to 46°F) or room temperature 20°C to 25°C (68°F to 77°F).
    Do not freeze
    .
  • The product does not contain a preservative. Discard unused vial after reconstitution if the recommended storage time is exceeded.

  Dilution in infusion bag

  • Withdraw the required volume of reconstituted solution from the ZYNLONTA vial using a sterile syringe. Discard any unused portion left in the vial.
  • Add the calculated dose volume of ZYNLONTA solution into a 50 mL infusion bag of
    5% Dextrose Injection, USP
    .
  • Gently mix the intravenous bag by slowly inverting the bag.
    Do not shake
    .
  • If not used immediately, store the diluted ZYNLONTA infusion solution refrigerated at 2°C to 8°C (36°F to 46°F) for up to 24 hours or at room temperature 20°C to 25°C (68°F to 77°F) for up to 8 hours. Discard diluted infusion bag if storage time exceeds these limits.
    Do not freeze.
  • No incompatibilities have been observed between ZYNLONTA and intravenous infusion bags with product-contacting materials of polyvinylchloride (PVC), polyolefin (PO), and PAB^®(copolymer of ethylene and propylene).

  Administration

  • Administer by intravenous infusion over 30 minutes using a dedicated infusion line equipped with a sterile, non-pyrogenic, low-protein binding in-line or add-on filter (0.2- or 0.22-micron pore size) and catheter.
  • Extravasation of ZYNLONTA has been associated with irritation, swelling, pain, and/or tissue damage, which may be severe
    [see Adverse Reactions (6.1)]
    . Monitor the infusion site for possible subcutaneous infiltration during drug administration.
  • Do not mix ZYNLONTA with or administer as an infusion with other drugs.
  )

For Injection: 10 mg of loncastuximab tesirine-lpyl as a white to off-white lyophilized powder in a single-dose vial for reconstitution and further dilution.

• Lactation: Advise not to breastfeed. (
  8.2 Lactation

  Risk Summary

  There is no data on the presence of loncastuximab tesirine-lpyl or SG3199 in human milk, the effects on the breastfed child, or milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with ZYNLONTA and for 3 months after the last dose.
  )

• Effusion and Edema
  : Monitor for the development of pleural effusion, pericardial effusion, ascites, peripheral edema, and general edema. Consider diagnostic imaging when symptoms develop or worsen. (
  5.1 Effusion and Edema

  Serious effusion and edema occurred in patients treated with ZYNLONTA. Grade 3 edema occurred in 3% (primarily peripheral edema or ascites) and Grade 3 pleural effusion occurred in 3% and Grade 3 or 4 pericardial effusion occurred in 1%

  [see Adverse Reactions (6.1)]

  .

  Monitor patients for new or worsening edema or effusions. Withhold ZYNLONTA for Grade 2 or greater edema or effusion until the toxicity resolves. Consider diagnostic imaging in patients who develop symptoms of pleural effusion or pericardial effusion, such as new or worsened dyspnea, chest pain, and/or ascites such as swelling in the abdomen and bloating. Institute appropriate medical management for edema or effusions

  [see Dosage and Administration (2.3)]

  .
  )
• Myelosuppression
  : Monitor blood cell counts. Withhold, reduce, or discontinue ZYNLONTA based on severity. (
  5.2 Myelosuppression

  Treatment with ZYNLONTA can cause serious or severe myelosuppression, including neutropenia, thrombocytopenia, and anemia. Grade 3 or 4 neutropenia occurred in 32%, thrombocytopenia in 20%, and anemia in 12% of patients. Grade 4 neutropenia occurred in 21% and thrombocytopenia in 7% of patients. Febrile neutropenia occurred in 3%

  [see Adverse Reactions (6.1)].

  Monitor complete blood counts throughout treatment. Cytopenias may require interruption, dose reduction, or discontinuation of ZYNLONTA. Consider prophylactic granulocyte colony-stimulating factor administration as applicable

  [see Dosage and Administration (2.3)].
  )
• Infections
  : Monitor for infection and treat promptly. (
  5.3 Infections

  Fatal and serious infections, including opportunistic infections, occurred in patients treated with ZYNLONTA. Grade 3 or higher infections occurred in 10% of patients, with fatal infections occurring in 2%. The most frequent Grade ≥3 infections included sepsis and pneumonia

  [see Adverse Reactions (6.1)]

  .

  Monitor for any new or worsening signs or symptoms consistent with infection. For Grade 3 or 4 infection, withhold ZYNLONTA until infection has resolved

  [see Dosage and Administration (2.3)]

  .
  )
• Cutaneous Reactions
  : Monitor patients for new or worsening cutaneous reactions, including photosensitivity reactions. Dermatologic consultation should be considered. (
  5.4 Cutaneous Reactions

  Serious cutaneous reactions occurred in patients treated with ZYNLONTA. Grade 3 cutaneous reactions occurred in 4% and included photosensitivity reaction, rash (including exfoliative and maculo-papular), and erythema

  [see Adverse Reactions (6.1)].

  Monitor patients for new or worsening cutaneous reactions, including photosensitivity reactions. Withhold ZYNLONTA for severe (Grade 3) cutaneous reactions until resolution

  [see Dosage and Administration (2.3)]

  . Advise patients to minimize or avoid exposure to direct natural or artificial sunlight including exposure through glass windows. Instruct patients to protect skin from exposure to sunlight by wearing sun-protective clothing and/or the use of sunscreen products. If a skin reaction or rash develops, dermatologic consultation should be considered

  [see Nonclinical Toxicology (13)].
  )
• Embryo-Fetal Toxicity
  : Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. (
  5.5 Embryo-Fetal Toxicity

  Based on its mechanism of action, ZYNLONTA can cause embryo-fetal harm when administered to a pregnant woman because it contains a genotoxic compound (SG3199) and affects actively dividing cells.

  Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ZYNLONTA and for 10 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ZYNLONTA, and for 7 months after the last dose

  [see Use in Specific Populations (8.1, 8.3)]

  .
  ,
  8.1 Pregnancy

  Risk Summary

  Based on its mechanism of action, ZYNLONTA can cause embryo-fetal harm when administered to a pregnant woman, because it contains a genotoxic compound (SG3199) and affects actively dividing cells

  [see Clinical Pharmacology (12.1)

  and

  Nonclinical Toxicology (13.1)]

  . There are no available data on the use of ZYNLONTA in pregnant women to evaluate for drug-associated risk. No animal reproduction studies were conducted with ZYNLONTA. Advise pregnant women of the potential risk to a fetus

  .

  The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

  Data

  Animal Data

  Animal reproductive or developmental toxicity studies were not conducted with loncastuximab tesirine-lpyl. The cytotoxic component of ZYNLONTA, SG3199, crosslinks DNA, is genotoxic, and is toxic to rapidly dividing cells, suggesting it has the potential to cause embryotoxicity and teratogenicity.
  ,
  8.3 Females and Males of Reproductive Potential

  ZYNLONTA can cause fetal harm when administered to pregnant women

  [see Use in Specific Populations (8.1)]

  .

  Pregnancy Testing

  Pregnancy testing is recommended for females of reproductive potential prior to initiating ZYNLONTA.

  Contraception

  Females

  Advise women of reproductive potential to use effective contraception during treatment and for 10 months after the last dose.

  Males

  Because of the potential for genotoxicity, advise males with female partners of reproductive potential to use effective contraception during the treatment with ZYNLONTA and for 7 months after the last dose

  [see Nonclinical Toxicology (13.1)]

  .

  Infertility

  Males

  Based on the results from animal studies, ZYNLONTA may impair fertility in males. The effects were not reversible in male cynomolgus monkeys during the 12-week drug-free period

  [see Nonclinical Toxicology (13.1)]

  .
  )