Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: ADC Therapeutics (NL) B.V., Laarderhoogtweg 25, Amsterdam, Noord-Holland, 1101 EB, Netherlands
Zynlonta as monotherapy is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL), after two or more lines of systemic therapy.
Zynlonta must only be administered under the supervision of a healthcare professional experienced in the diagnosis and treatment of cancer patients.
The recommended dose of Zynlonta is 0.15 mg/kg every 21 days for 2 cycles, followed by 0.075 mg/kg every 21 days for subsequent cycles until disease progression or unacceptable toxicity.
Unless contraindicated, dexamethasone 4 mg is to be administered orally or intravenously twice daily for 3 days, beginning the day before administering Zynlonta to mitigate pyrrolobenzodiazepine (PBD)-related toxicities. If dexamethasone administration does not begin the day before Zynlonta, oral or intravenous dexamethasone should begin at least 2 hours prior to administration of Zynlonta.
If a planned dose of Zynlonta is missed, it should be administered as soon as possible, and the schedule of administration should be adjusted to maintain a 21-day interval between doses.
For dose modification for haematologic and nonhaematologic adverse reactions (see section 4.8), see Table 1 below.
Table 1. Zynlonta dose modification for haematologic and nonhaematologic adverse reactions:
| Adverse reactions | Severity | Dose modification |
|---|---|---|
| Haematologic adverse reactions | ||
| Neutropenia (see section 4.8) | Absolute neutrophil count less than 1 × 109/L | Withhold Zynlonta until neutrophil count returns to 1 × 109/L or higher |
| Thrombocytopenia (see section 4.8) | Platelet count less than 50,000/mcL | Withhold Zynlonta until platelet count returns to 50,000/mcL or higher |
| Nonhaematologic adverse reactions | ||
| Oedema or effusion (see section 4.8) | Grade 2 or higher | Withhold Zynlonta until the toxicity resolves to Grade 1 or less |
| Other adverse reactions (see section 4.8) | Grade 3 or higher | Withhold Zynlonta until the toxicity resolves to Grade 1 or less |
If dosing is delayed by more than 3 weeks due to toxicity related to Zynlonta, subsequent doses should be reduced by 50%. If toxicity requires dose reduction following the second dose of 0.15 mg/kg (Cycle 2), the patient should receive the dose of 0.075 mg/kg for Cycle 3.
If toxicity reoccurs after two dose reductions following an adverse reaction, permanent discontinuation of Zynlonta should be considered.
No dose adjustment of Zynlonta is required in patients ≥65 years of age (see section 5.1).
No dose adjustment of Zynlonta is required for patients with mild to moderate renal impairment (see section 5.2).
Zynlonta has not been studied in patients with severe renal impairment (CLcr 15 to 29 mL/min). The effect of severe renal impairment, and end-stage renal disease, with or without haemodialysis, on loncastuximab tesirine pharmacokinetics is unknown. Additional monitoring for adverse reactions may be warranted in these patients when loncastuximab tesirine is administered.
For SG3199, data collected in an animal model (rat) show minimal renal excretion. No clinical data are available.
No dose adjustment is recommended for patients with mild hepatic impairment (total bilirubin ≤ upper limit of normal [ULN] and aspartate aminotransferase [AST] > ULN or total bilirubin >1 to 1.5 × ULN and any AST).
Zynlonta has not been studied in patients with moderate or severe hepatic impairment (total bilirubin >1.5 × ULN and any AST).
In patients with hepatic impairment, monitoring for adverse reactions is recommended.
The safety and efficacy of loncastuximab tesirine in children and adolescents aged less than 18 years have not yet been established. No data are available.
Zynlonta is for intravenous use.
The infusion is administered over 30 minutes through an intravenous line.
Extravasation of Zynlonta has been associated with irritation, swelling, pain, and/or tissue damage, which may be severe (see section 4.8). The infusion site should be monitored for possible subcutaneous infiltration during medicinal product administration.
Zynlonta must be reconstituted and diluted using aseptic technique under the supervision of a healthcare professional. It must be administered 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 micrometre pore size) and catheter.
For instructions on reconstitution and dilution of the medicinal product before administration, see section 6.6.
This medicinal product contains a cytotoxic component, which is covalently attached to the monoclonal antibody (see special handling and disposal procedures in section 6.6).
Symptomatic treatment and standard supportive care measures for the management of any observed toxicity should be applied.
Unopened vial:
3 years
Reconstituted solution:
From a microbiological point of view, the reconstituted solution should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and should not be longer than 4 hours refrigerated (2°C-8°C) or 4 hours at room temperature (20°C-25°C), unless reconstitution has taken place in controlled and validated aseptic conditions. Chemical and physical in-use stability of the reconstituted solution has been demonstrated for up to 4 hours refrigerated (2°C-8°C) or 4 hours at room temperature (20°C-25°C).
Diluted solution:
From a microbiological point of view, the prepared solution for infusion should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and should not be longer than 24 hours refrigerated (2°C-8°C) or 8 hours at room temperature (20°C-25°C), unless dilution has taken place in controlled and validated aseptic conditions. Chemical and physical in-use stability of the prepared solution for infusion has been demonstrated for up to 24 hours at room temperature (20°C-25°C).
Do not use the medicinal product if the storage conditions exceed the limits.
Store in a refrigerator (2°C–8°C).
Do not freeze.
Keep the vial in the outer carton in order to protect from light.
For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.
Vial (clear Type 1 glass) closed with a stopper (teflon coated rubber), with an aluminium seal with plastic flip-off cap containing 10 mg loncastuximab tesirine. Pack size of one vial.
Zynlonta contains a cytotoxic component and should be administered under the supervision of a physician experienced in the use of cytotoxic agents. Procedures for proper handling and disposal of antineoplastic and cytotoxic medicinal products should be used.
Proper aseptic technique throughout the handling of this medicinal product should be followed.
The reconstituted product contains no preservative and is intended for single-dose only.
Zynlonta must be reconstituted using sterile water for injections and diluted into an intravenous infusion bag containing 5% glucose prior to administration.
Both the reconstituted solution and the diluted solution for infusion should not be frozen or exposed to direct sunlight.
Calculate the total dose (mg) required based on the patient’s weight and prescribed dose (see section 4.2).
Zynlonta is for single-use only.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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