Introduction

Antineoplastic agent; a CD19-directed antibody-drug conjugate consisting of a humanized monoclonal IgG₁ kappa antibody linked to an alkylating agent (SG3199).

Uses for Loncastuximab

B-cell Lymphoma

Treatment of relapsed or refractory large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma, previously treated with ≥2 systemic therapies (designated an orphan drug by FDA for this use).

Efficacy based on overall response rate; clinical benefit (e.g., improvement in survival, amelioration of disease-related symptoms) not established.

Loncastuximab Dosage and Administration

General

Pretreatment Screening

• Verify pregnancy status of females of reproductive potential.

Patient Monitoring

• Monitor for extravasation and subcutaneous infiltration during administration of loncastuximab tesirine.

• Monitor for new or worsening effusions or edema.

• Evaluate for new or worsening signs or symptoms of infection.

• Monitor CBC during therapy.

• Monitor for new or worsening cutaneous reactions, including photosensitivity reactions.

Premedication and Prophylaxis

• Unless contraindicated, administer dexamethasone 4 mg orally or IV twice daily for 3 days beginning the day prior to day 1 of each cycle. If dexamethasone cannot be administered the day prior to day 1 of each cycle, administer dexamethasone at least 2 hours prior to administration of loncastuximab tesirine.

• Consider prophylaxis with a granulocyte colony-stimulating factor (G-CSF) as appropriate to reduce the risk of hematologic toxicity associated with loncastuximab tesirine therapy.

Dispensing and Administration Precautions

Handling and Disposal

• Loncastuximab tesirine is a hazardous drug; follow procedures for proper handling (e.g., use of gloves or protective clothing) and disposal of antineoplastic agents.

Administration

IV Administration

Administer via IV infusion. Loncastuximab tesirine lyophilized powder for injection must be reconstituted and diluted prior to administration.

Compatible with infusion bags containing polyvinylchloride (PVC), polyolefin (PO), and PAB (copolymer of ethylene and propylene). Administer final diluted solution through a 0.2 or 0.22-µm inline or add-on filter and catheter.

Do not mix with any other drug or administer any other drug simultaneously in the same IV line.

Reconstitution

Reconstitute vial containing 10 mg of loncastuximab tesirine with 2.2 mL of sterile water for injection to provide a solution containing 5 mg/mL; direct diluent toward the wall of the vial. Gently swirl vial to ensure dissolution. Do not shake reconstituted solution.

Reconstituted solution should be clear to slightly opalescent, colorless to slightly yellow in color, and free of visible particulates. Use within 4 hours of reconstitution.

Protect from direct sunlight until time of use; do not freeze.

Discard partially used vials.

Dilution

Dilute appropriate dose in 50 mL of 5% dextrose. Mix the diluted solution by gentle inversion.

Use diluted solution immediately or store at 2–8°C for up to 24 hours or at 20–25°C for up to 8 hours.

Rate of Administration

Administer by IV infusion over 30 minutes.

Dosage

Adults

Body mass index <35 kg/m²: Calculate dosage based on actual body weight.

Body mass index ≥35 kg/m²: Calculate dosage based on adjusted body weight using the following formula:

Adjusted body weight (in kg) = 35 kg/m² × (height in meters)².

B-cell Lymphoma

IV

Cycles 1 and 2: 0.15 mg/kg once on day 1 of each 21-day cycle

Subsequent cycles: 0.075 mg/kg on day 1 of each 21-day cycle.

Dosage Modification for Toxicity

Some adverse effects require temporary interruption and/or dosage reduction or discontinuance of therapy.

If toxicity delays administration by >3 weeks, reduce subsequent doses of loncastuximab tesirine by 50%. However, if dosage reduction is necessary after cycles 1 and 2 of loncastuximab tesirine 0.15 mg/kg, the patient should receive 0.075 mg/kg for cycle 3 onward.

Consider discontinuing therapy if toxicity recurs after dosage reduction.

Hematologic Toxicity

If ANC is <1000/mm³ or platelet count is <50,000/mm³, withhold loncastuximab tesirine until recovery of ANC ≥1000/mm³ or platelet count ≥50,000/mm³.

Edema or Effusion

If edema or effusion of grade 2 or higher occurs, withhold loncastuximab tesirine therapy until toxicity resolves to grade 1 or lower.

Other Adverse Reactions

If grade 3 or higher nonhematologic adverse reactions occur, withhold loncastuximab tesirine until toxicity resolves to grade 1 or lower, then resume therapy.

Special Populations

Dosage in Hepatic Impairment

Mild hepatic impairment (bilirubin concentration not exceeding ULN with AST concentration exceeding the ULN, or bilirubin concentration <1–1.5 times ULN with any AST concentration): No dosage adjustment required.

Moderate or severe hepatic impairment (bilirubin concentration >1.5 times ULN with any AST concentration): No recommended dose established.

Dosage in Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Contraindications

• None.

Warnings/Precautions

Effusion and Edema

Grade 3 edema (most commonly ascites or peripheral edema) and pleural effusion reported.

Initiate medical management if grade 2 or higher edema or effusion occur; withhold loncastuximab tesirine until resolved.

Diagnostic imaging may be necessary in patients experiencing symptoms of pleural or pericardial effusion.

Myelosuppression

Grade 3 or 4 anemia, neutropenia, and thrombocytopenia.

Monitor CBC during treatment with loncastuximab tesirine and consider prophylactic G-CSF as appropriate. May need to interrupt therapy, reduce dose, and/or permanently discontinue loncastuximab tesirine depending on severity and persistence of myelosuppression.

Infectious Complications

Serious infections reported in 10% of patients receiving loncastuximab tesirine-lpyl in clinical trials; 2% of serious infections have been fatal. Pneumonia and sepsis were the most frequently reported infections.

Monitor for signs and symptoms of infection during treatment with loncastuximab tesirine. If grade 3 or 4 infection occurs, withhold loncastuximab tesirine until infection resolves, then resume therapy.

Cutaneous Reactions

Severe cutaneous reactions, including erythema, photosensitivity, and rash (including maculopapular and exfoliative rash) reported.

Monitor for new or worsening cutaneous reactions, including photosensitivity reactions, during treatment with loncastuximab tesirine. If cutaneous reactions or rash develop, consider dermatologic consultation.

Advise patients to minimize or avoid direct natural or artificial sunlight (including exposure through glass windows); patients should wear sun-protective clothing or use sunscreen. May need to interrupt therapy, reduce dose, and/or permanently discontinue loncastuximab tesirine depending on severity and persistence of severe cutaneous reaction.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm.

SG3199 may cause embryotoxic and fetotoxic effects.

Advise pregnant females of the potential risk to the fetus. Advise females of reproductive potential and males who are partners of such females to use an effective method of contraception while receiving the drug and for 9 or 6 months, respectively, after the last dose.

Specific Populations

Pregnancy

May cause fetal harm.

Lactation

Unknown whether loncastuximab is distributed into milk in humans.

Discontinue breast-feeding during therapy and for 3 months following the last dose.

Females and Males of Reproductive Potential

Verify pregnancy status of females of reproductive potential prior to initiating therapy. Advise females of reproductive potential and males who are partners with such females to use an effective method of contraception during therapy and for 9 or 6 months, respectively, after the last dose.

May impair male fertility.

Pediatric Use

Safety and efficacy not established in pediatric patients.

Geriatric Use

No overall differences in safety or efficacy relative to younger adults.

Hepatic Impairment

Pharmacokinetics of loncastuximab tesirine is not affected by mild hepatic impairment (bilirubin concentration not exceeding ULN with AST concentration exceeding ULN, or bilirubin concentration <1–1.5 times ULN with any AST concentration); however, exposure to unconjugated SG3199 may be increased.

Data are not available for patients with moderate (bilirubin concentration >1.5-3 times ULN with any AST concentration) or severe (bilirubin >3 times ULN with any AST concentration) hepatic impairment.

Renal Impairment

Pharmacokinetics not affected by mild or moderate renal impairment (Cl_cr ≥30 mL/min).

Not studied in patients with severe renal impairment (Cl_cr <30 mL/min) or in patients with end-stage renal disease, including those undergoing dialysis.

Common Adverse Effects

Adverse effects occurring in ≥20% of patients receiving loncastuximab tesirine include thrombocytopenia , increased gamma-glutamyltransferase , neutropenia, anemia , hyperglycemia , elevated concentrations of aminotransferase , fatigue , hypoalbuminemia , rash , edema , nausea , and musculoskeletal pain.

General

Pretreatment Screening

• Verify pregnancy status of females of reproductive potential.

Patient Monitoring

• Monitor for extravasation and subcutaneous infiltration during administration of loncastuximab tesirine.

• Monitor for new or worsening effusions or edema.

• Evaluate for new or worsening signs or symptoms of infection.

• Monitor CBC during therapy.

• Monitor for new or worsening cutaneous reactions, including photosensitivity reactions.

Premedication and Prophylaxis

• Unless contraindicated, administer dexamethasone 4 mg orally or IV twice daily for 3 days beginning the day prior to day 1 of each cycle. If dexamethasone cannot be administered the day prior to day 1 of each cycle, administer dexamethasone at least 2 hours prior to administration of loncastuximab tesirine.

• Consider prophylaxis with a granulocyte colony-stimulating factor (G-CSF) as appropriate to reduce the risk of hematologic toxicity associated with loncastuximab tesirine therapy.

Dispensing and Administration Precautions

Handling and Disposal

• Loncastuximab tesirine is a hazardous drug; follow procedures for proper handling (e.g., use of gloves or protective clothing) and disposal of antineoplastic agents.

Administration

IV Administration

Administer via IV infusion. Loncastuximab tesirine lyophilized powder for injection must be reconstituted and diluted prior to administration.

Compatible with infusion bags containing polyvinylchloride (PVC), polyolefin (PO), and PAB (copolymer of ethylene and propylene). Administer final diluted solution through a 0.2 or 0.22-µm inline or add-on filter and catheter.

Do not mix with any other drug or administer any other drug simultaneously in the same IV line.

Reconstitution

Reconstitute vial containing 10 mg of loncastuximab tesirine with 2.2 mL of sterile water for injection to provide a solution containing 5 mg/mL; direct diluent toward the wall of the vial. Gently swirl vial to ensure dissolution. Do not shake reconstituted solution.

Reconstituted solution should be clear to slightly opalescent, colorless to slightly yellow in color, and free of visible particulates. Use within 4 hours of reconstitution.

Protect from direct sunlight until time of use; do not freeze.

Discard partially used vials.

Dilution

Dilute appropriate dose in 50 mL of 5% dextrose. Mix the diluted solution by gentle inversion.

Use diluted solution immediately or store at 2–8°C for up to 24 hours or at 20–25°C for up to 8 hours.

Rate of Administration

Administer by IV infusion over 30 minutes.

Dosage

Adults

Body mass index <35 kg/m²: Calculate dosage based on actual body weight.

Body mass index ≥35 kg/m²: Calculate dosage based on adjusted body weight using the following formula:

Adjusted body weight (in kg) = 35 kg/m² × (height in meters)².

B-cell Lymphoma

IV

Cycles 1 and 2: 0.15 mg/kg once on day 1 of each 21-day cycle

Subsequent cycles: 0.075 mg/kg on day 1 of each 21-day cycle.

Dosage Modification for Toxicity

Some adverse effects require temporary interruption and/or dosage reduction or discontinuance of therapy.

If toxicity delays administration by >3 weeks, reduce subsequent doses of loncastuximab tesirine by 50%. However, if dosage reduction is necessary after cycles 1 and 2 of loncastuximab tesirine 0.15 mg/kg, the patient should receive 0.075 mg/kg for cycle 3 onward.

Consider discontinuing therapy if toxicity recurs after dosage reduction.

Hematologic Toxicity

If ANC is <1000/mm³ or platelet count is <50,000/mm³, withhold loncastuximab tesirine until recovery of ANC ≥1000/mm³ or platelet count ≥50,000/mm³.

Edema or Effusion

If edema or effusion of grade 2 or higher occurs, withhold loncastuximab tesirine therapy until toxicity resolves to grade 1 or lower.

Other Adverse Reactions

If grade 3 or higher nonhematologic adverse reactions occur, withhold loncastuximab tesirine until toxicity resolves to grade 1 or lower, then resume therapy.

Special Populations

Dosage in Hepatic Impairment

Mild hepatic impairment (bilirubin concentration not exceeding ULN with AST concentration exceeding the ULN, or bilirubin concentration <1–1.5 times ULN with any AST concentration): No dosage adjustment required.

Moderate or severe hepatic impairment (bilirubin concentration >1.5 times ULN with any AST concentration): No recommended dose established.

Dosage in Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

SG3199 (small molecule cytotoxic component of loncastuximab tesirine) is metabolized by CYP3A4 and 3A5.

SG3199: Substrate of P-glycoprotein. Not a substrate of breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1, or organic cation transporter (OCT) 1. Does not inhibit CYP isoenzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4, and 3A5, P-gp, BCRP, OATP1B1, OATP1B3, organic anion transporter (OAT) 1, OAT3, OCT2, OCT1, multi-antimicrobial extrusion protein (MATE) 1, MATE2-K, or bile salt export pump (BSEP).