Version May 2024
Large B-cell lymphoma, relapsed or refractory: IV: 0.15 mg/kg on day 1 every 3 weeks for 2 cycles, followed by 0.075 mg/kg on day 1 every 3 weeks until disease progression or unacceptable toxicity (Ref). Note: For patients with a BMI ≥35 kg/m2, refer to "Dosing: Obesity: Adult."
Premedication: Administer dexamethasone 4 mg (IV or oral) twice daily for 3 days beginning the day before loncastuximab tesirine; if dexamethasone is not administered the day before, begin dexamethasone at least 2 hours prior to loncastuximab tesirine.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Kidney function estimated using the Cockcroft-Gault equation.
CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling; however, loncastuximab tesirine has minimal renal excretion and CrCl 30 to 89 mL/minute had no clinically significant difference on loncastuximab tesirine pharmacokinetics.
CrCl 15 to 29 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
End-stage renal disease (with or without hemodialysis): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Mild impairment (total bilirubin ≤ ULN and AST > ULN or total bilirubin >1 to 1.5 times ULN and any AST): No dosage adjustment necessary. Monitor for potential increased incidence of adverse drug reactions and modify the dosage if adverse reactions occur.
Moderate (total bilirubin >1.5 to ≤3 times ULN and any AST) or severe (total bilirubin >3 times ULN and any AST) impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
For patients with a BMI ≥35 kg/m2, the dose should be calculated based on an adjusted body weight (AdjBW). The following formula was used in the clinical trial and is recommended in the manufacturer's labeling: AdjBW in kg = 35 kg/m2 × (height in meters)2 (Ref). The adjusted dosing accounts for the risk of severe toxicities with weight-normalized calculations, cumulative toxicity (in a phase 1 study) in patients who received doses >0.15 mg/kg, and body weight as a significant covariate in a loncastuximab tesirine population pharmacokinetic analysis (Ref).
Loncastuximab tesirine dose reduction levels: If dosing is delayed by >3 weeks due to drug-related toxicity, reduce subsequent doses by 50%. If toxicity recurs following dose reduction, consider discontinuing loncastuximab tesirine. If toxicity requires a dose reduction following the second dose of 0.15 mg/kg (cycle 2), the dose in cycle 3 should be 0.075 mg/kg.
|
Adverse reaction |
Severity |
Dosage modification |
|---|---|---|
|
a Advise patients to minimize or avoid exposure to direct natural or artificial sunlight (including exposure through glass windows). Instruct patients to wear sun-protective clothing and/or use sunscreen. | ||
|
Hematologic adverse reactions | ||
|
Neutropenia |
ANC <1,000/mm3 |
Withhold loncastuximab tesirine until ANC returns to ≥1,000/mm3. Consider WBC growth factor support as indicated. |
|
Thrombocytopenia |
Platelets <50,000/mm3 |
Withhold loncastuximab tesirine until platelets return to ≥50,000/mm3. |
|
Nonhematologic adverse reactions | ||
|
Cutaneous reactionsa |
Skin reaction or rash |
Consider a dermatology consultation. |
|
Grade 3 (severe) |
Withhold loncastuximab tesirine until resolution. | |
|
Edema or effusion |
Symptoms of pleural effusion or pericardial effusion (eg, new or worsened dyspnea, chest pain) and/or ascites (eg, abdominal swelling, bloating) |
Consider diagnostic imaging. Institute appropriate medical management for edema or effusions. |
|
Grade 2 or higher |
Withhold loncastuximab tesirine until toxicity resolves to ≤ grade 1. | |
|
Infection |
Grade 3 or 4 |
Withhold loncastuximab tesirine until infection has resolved. |
|
Other adverse reactions |
Grade 3 or higher |
Withhold loncastuximab tesirine until toxicity resolves to ≤ grade 1. |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
>10%:
Cardiovascular: Edema (28%)
Dermatologic: Pruritus (12%), skin rash (30%)
Endocrine & metabolic: Decreased serum albumin (37%), increased serum glucose (48%)
Gastrointestinal: Abdominal pain (14%), constipation (12%), decreased appetite (15%), diarrhea (17%; grade 3: 2%), nausea (23%), vomiting (13%)
Hematologic & oncologic: Anemia (grades 3/4: 12%), neutropenia (grades 3/4: 21% to 32%), thrombocytopenia (grades 3/4: 7% to 20%)
Hepatic: Increased gamma-glutamyl transferase (57%), increased serum alanine aminotransferase (34%), increased serum aspartate aminotransferase (41%)
Nervous system: Fatigue (38%; including asthenia)
Neuromuscular & skeletal: Musculoskeletal pain (23%)
Respiratory: Dyspnea (13%)
1% to 10%:
Cardiovascular: Pericardial effusion (3%), pericarditis (≤3%), peripheral edema (grade 3: ≤3%)
Dermatologic: Dermatitis (≤3%), hyperpigmentation (4%), severe dermatological reaction (grade 3: ≤4%; including erythema of skin, exfoliative dermatitis, and maculopapular rash), skin photosensitivity (10%)
Hematologic & oncologic: Febrile neutropenia (3%)
Hepatic: Ascites (grade 3: ≤3%)
Infection: Sepsis (2%)
Respiratory: Pleural effusion (grade 3: 10%), pleurisy (≤3%), pneumonia (5%), pneumonitis (≤3%), upper respiratory tract infection (10%)
Frequency not defined: Infection: Opportunistic infection, serious infection
Postmarketing: Dermatologic: Skin blister, telangiectasia, vesicular eruption
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Bone marrow suppression: Loncastuximab tesirine may cause serious or severe hematologic toxicity, including neutropenia, thrombocytopenia, and anemia. Grade 3 or 4 events and neutropenic fever have occurred.
• Dermatologic toxicity: Serious cutaneous reactions have occurred with loncastuximab tesirine, including grade 3 cutaneous reactions, rash (exfoliative and maculo-papular), and erythema.
• Effusion/edema: Serious effusion and edema have occurred with loncastuximab tesirine, primarily peripheral edema or ascites. Grade 3 edema and pleural effusion have been reported and grade 3 and 4 pericardial effusion has occurred.
• Extravasation: Irritant with vesicant-like properties; avoid extravasation. Infiltration of loncastuximab tesirine is associated with irritation, swelling, pain, and/or tissue damage. Monitor infusion site during administration.
• Infection: Serious and fatal infections, including opportunistic infections, have occurred with loncastuximab tesirine. The most frequent ≥ grade 3 infections included sepsis and pneumonia.
• Photosensitivity: Grade 3 photosensitivity reactions have occurred with loncastuximab tesirine. Advise patients to minimize or avoid exposure to direct natural or artificial sunlight (including exposure through glass windows) and to wear sun-protective clothing and/or use sunscreen.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Zynlonta: Loncastuximab tesirine-lpyl 10 mg (1 ea)
No
Solution (reconstituted) (Zynlonta Intravenous)
10 mg (per each): $31,560.01
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
IV: Infuse over 30 minutes using a dedicated infusion line with a sterile, nonpyrogenic, low-protein binding 0.2 or 0.22 micron in-line or add-on filter and catheter. Do not infuse with other medications.
Irritant with vesicant-like properties; avoid extravasation. Monitor infusion site during administration; loncastuximab tesirine is associated with irritation, swelling, pain, and/or tissue damage if extravasated.
Hazardous agent (NIOSH [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Large B-cell lymphoma, relapsed or refractory: Treatment of relapsed or refractory large B-cell lymphoma in adults 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.
Loncastuximab tesirine may be confused with brentuximab vedotin, cetuximab, dinutuximab, isatuximab, margetuximab, rituximab, and siltuximab.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Substrate of CYP3A4 (minor), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Evaluate pregnancy status prior to use in patients who could become pregnant.
Patients who could become pregnant should use effective contraception during therapy and for 10 months after the last loncastuximab tesirine dose. Patients with partners who could become pregnant should also use effective contraception during therapy and for 7 months after the last dose of loncastuximab tesirine.
Loncastuximab tesirine is a humanized monoclonal antibody (IgG1) conjugated to SG3199. Human IgG crosses the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Clements 2020; Palmeira 2012; Pentsuk 2009).
Based on the mechanism of action, in utero exposure to loncastuximab tesirine may cause fetal harm. The SG3199 component is cytotoxic and induces cell death in actively dividing cells.
It is not known if loncastuximab tesirine is present in breast milk.
Loncastuximab tesirine is a humanized monoclonal antibody (IgG1) conjugated to SG3199. Human IgG is present in breast milk; concentrations are dependent upon IgG subclass and postpartum age (Anderson 2021). Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends that breastfeeding be discontinued during therapy and for 3 months after the last dose of loncastuximab tesirine.
CBC (throughout treatment). Evaluate pregnancy status prior to use in patients who may become pregnant. Monitor for new or worsening edema or effusions and for signs/symptoms of infections or cutaneous adverse reactions. Monitor patients with mild hepatic impairment for adverse drug reactions Monitor infusion site during administration.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Loncastuximab tesirine is an antibody drug conjugate that contains a humanized IgG1 monoclonal antibody directed at CD19, conjugated to a pyrrolobenzodiazepine dimer cytotoxic alkylating agent (SG3199) via a protease cleavable linker (the linker with SG3199 attached is the small molecule cytotoxin, SG3249 [tesirine]). The antibody component binds to CD19 (a transmembrane protein expressed on B-cell surfaces). After binding, loncastuximab tesirine is internalized and releases SG3199 via proteolytic cleavage. SG3199 then binds to the DNA minor groove and forms highly cytotoxic DNA inter-strand crosslinks and induces cell death.
Onset: Median time to response: 1.3 months (range: 1.1 to 8.1 months).
Distribution: Vd: 7.11 L.
Metabolism: The monoclonal antibody portion is expected to be metabolized by catabolic pathways into small peptides. SG3199 is metabolized by CYP3A4/5 (in vitro).
Half-life elimination: ~21 days.
Excretion: SG3199 (the small molecule cytotoxin) has minimal renal excretion.
Clearance: 0.499 L/day (following a single dose); 0.275 L/day (at steady state).
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