Dosing & Uses
Dosage Forms & Strengths
injection, lyophilized powder for reconstitution
- 10mg/vial
Large B-Cell Lymphoma
Indicated for relapsed or refractory large B-cell lymphoma after ≥2 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
Cycles 1-2: 0.15 mg/kg IV q3Weeks
Cycle 3 and thereafter: 0.075 mg/kg IV q3Weeks
Dosage Modifications
If dosing delayed >3 week owing to toxicity, reduce subsequent doses by 50%; if toxicity reoccurs despite dose reduction, consider discontinuation
If toxicity requires dose reduction following second dose of 0.15 mg/kg (Cycle 2), reduce dose to 0.075 mg/kg for Cycle 3
Hematologic adverse effects
- Neutropenia (absolute neutrophil count [ANC] <1x 109/L): Withhold until ANC ≥1 x 109/L
- Thrombocytopenia (platelets [Plt] <50,000/mcL): Withhold until plt ≥50,000/mcL
Nonhematologic adverse effects
- Edema or effusion Grade ≥2: Withhold until resolves to Grade ≤1
- Other adverse effects Grade ≥3: Withhold until resolves to Grade ≤1
Renal impairment
- Minimally excreted via kidneys
- Mild-to-moderate (CrCl 30 to <90 mL/min): No clinically significant differences in pharmacokinetics observed
- Severe (CrCl 15-29 mL/min) and ESRD with or without hemodialysis: Pharmacokinetics unknown
Hepatic impairment
- Mild (total bilirubin [TB] ≤ULN and AST >ULN, or TB 1-1.5 x ULN and any AST): No dose adjustment recommended; monitor patients with mild hepatic impairment for potential increased incidence of adverse reactions and modify dosage as necessary
- Moderate or severe (TB >1.5 x ULN and any AST): Not studied
Dosing Considerations
Verify pregnancy status for females of reproductive potential before initiating
Safety and efficacy not established
Adverse Effects
>10%
All grades
- Platelets decreased (58%)
- GGT increased (57%)
- Neutrophils decreased (52%)
- Hemoglobin decreased (51%)
- Glucose increased (48%)
- AST increased (41%)
- Fatigue (38%)
- Albumin decreased (37%)
- ALT increased (34%)
- Rash (30%)
- Edema (28%)
- Musculoskeletal pain (23%)
- Nausea (23%)
- Diarrhea (17%)
- Decreased appetite (15%)
- Abdominal pain (14%)
- Dyspnea (13%)
- Vomiting (13%)
- Constipation (12%)
- Pruritus (12%)
Grades 3 or 4
- Neutrophils decreased (30%)
- GGT increased (21%)
- Platelets decreased (17%)
1-10%
All grades
- Photosensitivity (10%)
- Pleural effusion (10%)
- Upper respiratory tract infection (10%)
- Pneumonia (5%)
- Hyperpigmentation (4%)
- Febrile neutropenia (3%)
- Pericardial effusion (3%)
- Sepsis (2%)
Grades 3 or 4
- Hemoglobin decreased (10%)
- Glucose increased (8%)
- ALT increased (3%)
- Edema (3%)
- Abdominal pain (3%)
- Rash (2%)
- Photosensitivity (2%)
- Diarrhea (2%)
- Pleural effusion (2%)
- Fatigue (1%)
- Musculoskeletal pain (1%)
- Dyspnea (1%)
<1%
Infusion site extravasation
Upper respiratory tract infection (Grade 3 or 4)
AST increased (Grade 3)
Albumin decreased (Grade 3)
Postmarketing Reports
Skin and subcutaneous tissue disorders: Telangiectasia, blister, rash vesicular
Warnings
Contraindications
None
Cautions
Serious effusion and edema reported; consider diagnostic imaging for symptoms of pleural effusion or pericardial effusion (eg, new or worsened dyspnea, chest pain, and/or ascites [eg, abdominal swelling and bloating])
Can cause serious or severe myelosuppression, including neutropenia, thrombocytopenia, and anemia; monitor complete blood cell counts throughout treatment; cytopenias may require interruption, dose reduction, or discontinuation of drug; consider prophylactic granulocyte colony-stimulating factor administration as applicable
Fatal and serious infections, including opportunistic infections, reported; monitor for new or worsening signs or symptoms consistent with infection
Cutaneous reactions may occur, including photosensitivity reaction, rash (including exfoliative and maculopapular), and erythema; 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 skin reaction or rash develops, consider dermatologic consultation
Based on its mechanism of action, can cause embryofetal harm when administered to pregnant females; contains a genotoxic compound (SG3199) and affects actively dividing cells
Pregnancy & Lactation
Pregnancy
Based on its mechanism of action, can cause embryofetal harm when administered to pregnant females, because it contains SG3199 (a genotoxic compound that crosslinks DNA) and affects actively dividing cells
Advise pregnant females of the potential risk to fetus
Verify pregnancy status for females of reproductive potential before initiating
Contraception
- Females of reproductive potential: Use effective contraception during treatment and for 10 months after last dose
- Males with female partners of reproductive potential: Use effective contraception during treatment and for 7 months after last dose
Infertility
- Based on animal studies, may impair fertility in males
- Effects were not reversible in male cynomolgus monkeys during 12-week drug-free period
Lactation
Data are not available regarding presence in human milk, effects on breastfed children, or effects on milk production
Owing to potential for serious adverse reactions in breastfed children, advise females not to breastfeed during treatment and for 3 months after last dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Antibody-drug conjugate composed of a CD19-targeting antibody and pyrrolobenzodiazepine dimers
The monoclonal IgG1-kappa antibody component binds to human CD19, a transmembrane protein expressed on surface of cells of B-lineage origin
The small molecule component is SG3199, a PBD dimer and alkylating agent
Upon binding to CD19, loncastuximab tesirine is internalized, followed by release of SG3199 via proteolytic cleavage; released SG3199 binds to the DNA minor groove and forms highly cytotoxic DNA interstrand crosslinks, subsequently inducing cell death
Absorption
Steady-state reached at 210 days
Peak plasma concentration
- Cycle 2: 2,911 ng/mL
- Steady-state: 1,776 ng/mL
AUC
- Cycle 2: 21,665 ngday/mL
- Steady-state: 16,882 ngday/mL
Distribution
Vd: 7.11 L
Metabolism
Monoclonal antibody portion: Metabolized into small peptides by catabolic pathways
SG3199: Metabolized by CYP3A4/5 in vitro
Elimination
Half-life: 20.8 days (steady-state)
Clearance: 0.275 L/day (steady-state)
Excretion: Not studied in humans; SG3199 expected to be minimally excreted via kidneys
Administration
IV Incompatibilities
Do not mix with or administer as infusion with other drugs
IV Compatibilities
Dextrose 5% (D5W)
IV Preparation
Dose calculation
- Calculate the total dose (mg) required based on the patient’s weight and prescribed dose
- Convert calculated dose (mg) to volume using 5 mg/mL (concentration following reconstitution)
- More than 1 vial may be needed to achieve required dose
-
BMI ≥35 kg/m2
- Calculate the dose based on an adjusted body weight (ABW) as follows
- ABW in kg = 35 kg/m2 x (height in meters)2
Initial reconstitution
- Reconstitute each vial using 2.2 mL of sterile water for injection with the stream directed toward the inside vial wall to obtain final concentration of 5 mg/mL
- Do not shake; swirl vial gently until powder completely dissolved
- Do not expose to direct sunlight
- Inspect for particulate matter and discoloration; solution should appear clear to slightly opalescent, colorless to slightly yellow; do not use if discolored, cloudy, or contains visible particulates
- Use reconstituted immediately, or store as described below
Further dilution required
- Withdraw required volume of reconstituted solution from vial using a sterile syringe; discard any unused portion remaining
- Add calculated dose to 50 mL infusion bag of D5W
- Do not shake; gently mix IV bag by slowly inverting
IV Administration
Administer over 30 minutes using dedicated infusion line equipped with sterile, nonpyrogenic, low-protein–binding in-line or add-on filter (0.2- or 0.22-micron pore size) and catheter
Premedication
- Unless contraindicated, administer dexamethasone 4 mg PO/IV BID x3 days beginning the day before administering loncastuximab tesirine
- If dexamethasone not administered the day before, give dexamethasone at least 2 hr before administration
Extravasation
- Associated with irritation, swelling, pain, and/or tissue damage, which may be severe
- Monitor infusion site for possible SC infiltration during administration
Storage
Do not shake
Do not freeze vial, reconstituted vial, or diluted infusion bag
Follow applicable special handling and disposal procedures
Unopened vial
- Refrigerate at 2-8ºC (36-46ºF) in original carton to protect from light
Reconstituted vial
- Refrigerate at 2-8ºC (36-46ºF) or at room temperature of 20-25ºC (68-77ºF) for up to 4 hr
- Does not contain a preservative; discard unused vial after reconstitution if recommended storage time exceeded
Dilution in infusion bag
- Refrigerated at 2-8ºC (36-46ºF): Up to 24 hr
- Room temperature at 20-25ºC (68-77ºF): Up to 8 hr
- Does not contain a preservative; discard unused vial after reconstitution if recommended storage time exceeded
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