loncastuximab tesirine

Action and Spectrum

Actions and spectrum: 

• Targeted B-Cell Killing: loncastuximab tesirine specifically targets CD19-expressing B-cells, including malignant B-cells in various B-cell malignancies such as diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). It binds to CD19, leading to internalization of the antibody-drug conjugate into the cancer cells. 
• Cytotoxic Effect: Once internalized, loncastuximab tesirine releases the cytotoxic agent tesirine, which induces cell death by disrupting microtubule networks and inhibiting DNA synthesis. This mechanism helps to selectively kill CD19-positive B-cells, including cancer cells, while sparing normal cells to some extent. 
• Antitumor Activity: loncastuximab tesirine has demonstrated significant antitumor activity in clinical trials, showing durable responses and improved survival outcomes in patients with relapsed or refractory DLBCL and FL. 

The spectrum of loncastuximab tesirine primarily covers CD19-positive B-cell malignancies, providing a targeted and potent treatment option for patients who have relapsed or become refractory to other therapies. However, it is important to note that loncastuximab tesirine is indicated for specific B-cell malignancies as determined by healthcare providers and should be used under their guidance. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

All grades 

• Pleural effusion (10%) 
• Pneumonia (5%) 
• Febrile neutropenia (3%) 
• Sepsis (2%) 
• Photosensitivity (10%) 
• URTI (10%) 
• Hyperpigmentation (4%) 
• Pericardial effusion (3%) 

Grades 3 or 4 

• Glucose increased (8%) 
• Edema (3%) 
• Rash (2%) 
• Diarrhea (2%) 
• Fatigue (1%) 
• Dyspnea (1%) 
• Hemoglobin decreased (10%) 
• ALT increased (3%) 
• Abdominal pain (3%) 
• Photosensitivity (2%) 
• Pleural effusion (2%) 
• Musculoskeletal pain (1%)

>10% 

• increased GGT (57%) 
• decreased Hemoglobin (51%) 
• increased AST (41%) 
• decreased Albumin (37%) 
• Rash (30%) 
• Musculoskeletal pain (23%) 
• Diarrhea (17%) 
• Abdominal pain (14%) 
• Vomiting (13%) 
• decreased Platelets (58%) 
• Pruritus (12%) 
• decreased Neutrophils (52%) 
• increased Glucose (48%) 
• Fatigue (38%) 
• increased ALT (34%) 
• Edema (28%) 
• Nausea (23%) 
• Decreased appetite (15%) 
• Dyspnea (13%) 
• Constipation (12%)

<1% 

Infusion site extravasation 

URTI (Grade 3 or 4) 

Albumin decreased (Grade 3) 

AST increased (Grade 3)  

Post marketing Reports 

subcutaneous tissue and skin disorders: blister, Telangiectasia, rash vesicular 

Black Box Warning

Black Box Warning: 

there are no specific black box warnings associated with loncastuximab tesirine. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

There are no specific contraindications for loncastuximab tesirine  

Caution: 

• Infusion-related reactions: loncastuximab tesirine may cause infusion-related reactions, including fever, chills, nausea, vomiting, fatigue, headache, and allergic reactions. Close monitoring during and after the infusion is recommended, and appropriate medical management should be available. 
• Myelosuppression: loncastuximab tesirine can cause myelosuppression, including low WBC count, low platelet count, and low red blood cell count. Regular monitoring of blood cell counts is necessary, and appropriate supportive care should be provided as needed. 
• Infections: Treatment with loncastuximab tesirine may increase the risk of infections, including opportunistic infections. Vigilance for signs and symptoms of infection and prompt management are important. 
• Hepatotoxicity: loncastuximab tesirine has the potential to cause hepatotoxicity, including liver enzyme elevation and liver injury. Liver function tests should be performed regularly, and patients with pre-existing liver conditions may require additional monitoring. 
• Embryo-Fetal Toxicity: loncastuximab tesirine may cause fetal harm when administered to pregnant individuals. Adequate contraception should be used during treatment and for a certain period after the last dose.

Comorbidities: 

• Cardiovascular Diseases: Patients with pre-existing cardiovascular diseases, such as hypertension, congestive heart failure, or a history of myocardial infarction, may require careful monitoring during treatment with loncastuximab tesirine due to the potential for cardiovascular side effects. 
• Renal Impairment: Patients with pre-existing renal impairment may require dose adjustments or close monitoring of kidney function during treatment with loncastuximab tesirine, as the drug and its metabolites may be excreted through the kidneys. 
• Hepatic Impairment: Patients with pre-existing liver disease or impaired liver function may require caution and close monitoring when receiving loncastuximab tesirine due to the potential for hepatotoxicity and liver enzyme elevation. 
• Infections: Patients with a history of recurrent or chronic infections may require careful monitoring and appropriate prophylactic measures during treatment with loncastuximab tesirine due to the potential for increased susceptibility to infections. 
• Immunodeficiency: Patients with underlying immunodeficiency, such as HIV/AIDS or immunosuppressive therapy, may have an increased risk of complications during treatment with loncastuximab tesirine due to the potential for immunosuppression and increased susceptibility to infections. 

Pregnancy / Lactation

Pregnancy consideration: N/A 

Lactation: N/A  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

loncastuximab tesirine is a novel antibody-drug conjugate (ADC) that combines a monoclonal antibody targeting the CD19 antigen with a cytotoxic agent called tesirine. The pharmacology of loncastuximab tesirine involves both the antibody-mediated targeting of CD19-positive B cells and the cytotoxic activity of tesirine. 

The monoclonal antibody component of loncastuximab tesirine binds specifically to CD19, including malignant B cells in certain lymphomas. This antibody binding facilitates the internalization of the ADC into the target B cells. 

Once internalized, the linker connecting the antibody to tesirine is cleaved, releasing the cytotoxic agent. Tesirine, a DNA-alkylating pyrrolobenzodiazepine dimer, then exerts its cytotoxic effect by crosslinking DNA strands, leading to DNA damage and subsequent apoptosis (cell death) of the CD19-positive B cells.  

Pharmacodynamics: 

The pharmacodynamics of loncastuximab tesirine involve its mechanism of action and the effects it exerts on the targeted CD19-positive B cells. The drug exhibits both antibody-mediated effects and cytotoxic activity. 

• CD19 Targeting: loncastuximab tesirine specifically targets CD19, including malignant B cells. By binding to CD19, the drug enables selective targeting of CD19-positive B cells, including tumor cells. 
• Internalization and Cytotoxic Effect: Following CD19 binding, loncastuximab tesirine is internalized by the B cells. Within the B cells, the linker connecting the antibody to the cytotoxic agent tesirine is cleaved, releasing the cytotoxic payload. 
• DNA Damage and Apoptosis: The released tesirine, a DNA-alkylating pyrrolobenzodiazepine dimer, crosslinks DNA strands, leading to DNA damage within the targeted B cells. This DNA damage triggers apoptotic pathways, resulting in programmed cell death. 
• Tumor Cell Killing: By inducing apoptosis in CD19-positive B cells, loncastuximab tesirine contributes to the reduction of tumor burden and the elimination of malignant B cells. 

Pharmacokinetics: 

Absorption 

loncastuximab tesirine is administered intravenously, which allows for rapid and complete absorption of the drug into the bloodstream. As an intravenous formulation, it bypasses the need for gastrointestinal absorption. 

Distribution 

Once in the bloodstream, loncastuximab tesirine is distributed throughout the body to reach its target cells, which are CD19-positive B cells. The drug is expected to distribute similarly to other monoclonal antibodies within the systemic circulation. 

Metabolism 

The metabolism of loncastuximab tesirine involves the cleavage of the linker that connects the monoclonal antibody component to the cytotoxic agent, tesirine. This cleavage occurs within the CD19-positive B cells upon internalization of the drug. The cytotoxic agent tesirine is then released to exert its therapeutic effects. 

Elimination and excretion 

The elimination of loncastuximab tesirine and its metabolites primarily occurs through various mechanisms, including renal excretion, metabolic degradation, and clearance from the systemic circulation. The specific details of its elimination kinetics, such as half-life and clearance rate, are determined through clinical studies. 

Adminstartion

Administration: 

• Preparation: loncastuximab tesirine is supplied as a sterile lyophilized powder for reconstitution. It should be reconstituted and further diluted according to the instructions provided by the manufacturer. Proper aseptic techniques should be followed during preparation. 
• Intravenous Infusion: Once prepared, loncastuximab tesirine is administered as a slow intravenous infusion over a specified duration. The infusion rate and duration may vary depending on the specific treatment regimen. The healthcare provider will determine the appropriate infusion rate and closely monitor the patient during the infusion. 
• Pre-Medication: To mitigate the risk of infusion-related reactions, patients may receive pre-medication, such as antihistamines and corticosteroids, prior to the infusion of loncastuximab tesirine. This helps reduce the potential for allergic reactions or other infusion-related side effects. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: loncastuximab tesirine 

Pronounced: (lon-KAS-tux-i-mab teh-SIR-een)  

Why do we use loncastuximab tesirine? 

loncastuximab tesirine is a targeted therapy used for the treatment of certain types of lymphoma. It is specifically indicated for the following: 

• Refractory or Relapsed Diffuse Large B-Cell Lymphoma: loncastuximab tesirine is used as a single treatment for adult patients with Refractory or Relapsed DLBCL after at least two prior systemic therapies. It is typically used when other treatment options have been unsuccessful. 
• Relapsed or Refractory Follicular Lymphoma (FL): loncastuximab tesirine is also indicated for adult patients with refractory or relapsed FL who have received at least two prior systemic therapies. It is used in cases where other treatment options have not provided a satisfactory response.