Zynlonta

About Zynlonta (Loncastuximab tesirine-lpyl)

• Loncastuximab tesirine, marketed as Zynlonta, received accelerated approval from the FDA on April 23, 2021. 
• It is indicated for adult patients with relapsed or refractory large B-cell lymphoma after undergoing two or more lines of systemic therapy, including various forms of diffuse large B-cell lymphoma (DLBCL). 
• Loncastuximab tesirine is a CD19-directed antibody and alkylating agent conjugate with a distinctive mechanism of action. 
• This humanized monoclonal antibody is linked to a cytotoxic pyrrolobenzodiazepine (PBD) dimer via a cleavable linker. CD19, a protein abundantly expressed on B-cell hematological tumors, is specifically targeted by this antibody. 
• Upon binding to tumor cells, the antibody is internalized, releasing the cytotoxic PBD, which disrupts cancer cell division by crosslinking specific sites on DNA, ultimately leading to cell death. 
• This mechanism underscores the targeted and potent therapeutic effect of loncastuximab tesirine in relapsed or refractory large B-cell lymphoma treatment.

Strength: 

A single-dose vial contains 10 mg of loncastuximab tesirine-lpyl in lyophilized powder form, intended for reconstitution and subsequent dilution.

Recommended Dosage:

Administer the infusion over 30 minutes via a dedicated line equipped with a sterile, non-pyrogenic filter and monitor for extravasation and site reactions. Avoid mixing or co-administration with other drugs.

• The recommended dosage for Zynlonta involves intravenous infusion over a 30-minute period on Day 1 of each cycle, which occurs every 3 weeks. The infusion protocol is as follows: administer 0.15 mg/kg every 3 weeks for the initial 2 cycles, followed by 0.075 mg/kg every 3 weeks for subsequent cycles. 
• Additionally, it is advised to administer premedication with dexamethasone, unless contraindicated. Dexamethasone should be given at a dose of 4 mg orally or intravenously twice daily for 3 days, starting the day before administration. 
• If dexamethasone cannot be given on the day preceding Zynlonta, it should be initiated at least 2 hours prior to the administration.
• If dosing of Zynlonta is delayed by more than 3 weeks due to toxicity, subsequent doses should be reduced by 50%. If toxicity recurs despite dose reduction, discontinuation should be considered. 
• It’s important to note that if toxicity necessitates dose reduction after the second dose of 0.15 mg/kg (Cycle 2), the patient should receive the dose of 0.075 mg/kg for Cycle 3. Patients should consult their doctor for further information and guidance regarding their specific situation.

Important:

Your Zynlonta treatment may be adjusted by your healthcare provider in response to severe side effects, which could involve stopping or delaying treatment or altering the dose. Regular blood tests will be conducted to monitor for potential side effects. 

The number of treatments required will be determined based on your individual response to therapy. Before starting treatment, inform your doctor about your pregnancy status, plans for pregnancy, or breastfeeding, along with all current medications and medical conditions. This information allows your doctor to assess potential interactions and customize your treatment plan accordingly.

Warnings & Precautions

• Zynlonta treatment necessitates vigilant monitoring for several potential adverse effects. Keep a close watch for the development or exacerbation of pleural effusion, pericardial effusion, ascites, and peripheral, or general edema, considering diagnostic imaging when symptoms arise or worsen. 
• Additionally, be mindful of myelosuppression, which can manifest as neutropenia, thrombocytopenia, or anemia; regular monitoring of complete blood counts is imperative throughout treatment, with adjustments or discontinuation of the medicine as necessary based on severity. 
• Given the risk of serious or fatal infections, including opportunistic infections, promptly assess for signs of infection and initiate treatment when warranted. 
• Serious cutaneous reactions, including Grade 3 reactions such as photosensitivity, rash, and erythema, have been reported; thus, closely monitor patients for any new or worsening cutaneous issues, with consideration of dermatologic consultation if needed. 
• Lastly, due to the potential for embryo-fetal toxicity, advise patients of reproductive potential about the risks and the importance of effective contraception while on this drug, as it contains a genotoxic compound (SG3199) that can harm actively dividing cells and poses a risk to fetal development if administered during pregnancy.

Common Zynlonta Side Effects:

• Thrombocytopenia
• Increased gamma-glutamyltransferase
• Neutropenia
• Anemia
• Hyperglycemia
• Transaminase elevation
• Fatigue
• Hypoalbuminemia
• Rash
• Edema
• Nausea
• Musculoskeletal pain

Use in Specific Population

• Due to its mechanism of action, Zynlonta carries the risk of causing harm to the embryo or fetus if administered to pregnant women. 
• This risk arises from the presence of a genotoxic compound (SG3199) in the medication, which affects actively dividing cells. 
• There is currently no available data on whether loncastuximab tesirine-lpyl or SG3199 are present in human milk, their potential effects on breastfed infants, or their impact on milk production. 
• Therefore, it is advised that women refrain from breastfeeding while undergoing treatment with this medicine and for a period of 3 months after the last dose to avoid potential serious adverse reactions in breastfed infants. 
• Additionally, it has been associated with fetal harm when administered during pregnancy.
• Prior to initiating treatment it is recommended that females of reproductive potential undergo pregnancy testing. 
• Women of reproductive age should also use effective contraception during treatment and for a duration of 9 months following the last dose. 
• Similarly, males with female partners of reproductive potential should use effective contraception during Zynlonta treatment and for a period of 6 months after the last dose, due to the potential for genotoxicity.
• Animal studies suggest that this medicine may lead to impaired fertility in males, with effects observed in male cynomolgus monkeys being irreversible during a 12-week drug-free period. However, the safety and efficacy in pediatric patients have not been established.
• No notable differences in safety or effectiveness were observed between older patients and younger counterparts.
• For patients with mild hepatic impairment, no dose adjustment is recommended, although monitoring for potential increased adverse reactions is advised, with modifications to the Zynlonta dosage if necessary. However, this medicine has not been studied in patients with moderate or severe hepatic impairment.

Storage and Handling

• Keep Zynlonta stored in its original carton in a refrigerator at a temperature between 2°C to 8°C (36°F to 46°F) to shield it from light exposure. 
• Avoid freezing the medication.
• Do not freeze the medicine. 
• Keep the medicine away from pets and children.