lifileucel

Action and Spectrum

Actions and Spectrum 

Action: 

Collection: The drug starts with the collection of a patient’s own T-cells through a process called leukapheresis. Blood is drawn from the patient, and T-cells are separated and collected from the rest of the blood components. 

Genetic Modification: The collected T-cells are then genetically modified in the laboratory. This involves the introduction of a synthetic gene that encodes a chimeric antigen receptor (CAR) specific to a particular antigen present on the surface of cancer cells. 

Expansion: The modified T-cells are cultured and allowed to multiply in large numbers, generating a significant population of CAR T-cells. This expansion phase aims to obtain sufficient CAR T-cells for therapeutic administration. 

Infusion: The expanded CAR T-cells are then infused back into the patient’s bloodstream. The infused CAR T-cells travel throughout the body, seeking out and targeting cancer cells expressing the specific antigen recognized by the CAR. 

Targeting Cancer Cells: When the CAR T-cells encounter cancer cells expressing the target antigen, the CAR receptor binds to the antigen, initiating a series of signaling events within the CAR T-cells. 

Immune Response: The activation of CAR T-cells leads to the release of cytotoxic molecules, such as perforin and granzymes, which induce the death of the cancer cells. CAR T-cells also produce cytokines, such as interferon-gamma, which help recruit and activate other immune cells to join the attack against the cancer cells. 

Spectrum:  

The drug is designed to target and treat certain types of B-cell malignancies, particularly relapsed or refractory large B-cell lymphomas. These may include: 

<b>Diffuse Large B-cell Lymphoma (DLBCL): This is the most common type of non-Hodgkin lymphoma, characterized by rapidly growing lymph nodes.  

High-Grade B-cell Lymphoma: This is an aggressive form of B-cell lymphoma that may exhibit features similar to DLBCL.

Drug Interaction

Adverse Reaction

Frequency not defined  

Severe cytopenia

Internal organ hemorrhage

Severe infection

Cardiac disorders

Respiratory failure

Acute renal failure

Hypersensitivity reactions

Black Box Warning

Black Box Warning: 

The black box warning for Amtagvi includes the following:

Amtagvi (lifileucel) may cause severe and potentially life-threatening adverse reactions, including:

• Allergic reactions, including anaphylaxis: Patients should be monitored closely for signs of allergic reactions during and after administration. Immediate medical attention is necessary if anaphylaxis occurs.
• Fatal infections: Serious, life-threatening infections have been reported following Amtagvi administration. Patients should be evaluated for infections prior to treatment, and prophylactic antibiotics may be considered.
• Internal organ hemorrhage: Cases of internal organ bleeding, such as within the abdomen or skull, have been reported. Caution should be exercised in patients with a history of bleeding disorders or concurrent use of anticoagulants.
• Cytopenia and febrile neutropenia: Grade 3 or higher cytopenia and febrile neutropenia have been observed in a significant percentage of patients. Regular monitoring of blood counts is essential.
• Acute infusion reactions: Immediate infusion reactions, including fever, chills, rash, hypotension, dyspnea, cough, chest tightness, and wheezing, may occur. Patients should be closely monitored during and after infusion.
• Worsened respiratory and kidney function: Amtagvi has been associated with worsening respiratory and kidney function, which can be fatal. Patients should be monitored for changes in respiratory and renal status.

Contraindication / Caution

Contraindication/Caution:  

Hypersensitivity: The drug is contraindicated in individuals with a hypersensitivity or severe allergic reactions to any of the components of the drug formulation. Prior to administration, healthcare professionals should thoroughly assess patients for any history of hypersensitivity to prevent potential adverse reactions.  

Active Systemic Infections: The drug administration should be avoided in patients with active systemic infections. The drug’s mechanism of action involves stimulating of the immune system, which may exacerbate existing infections or compromise the body’s ability to fight off pathogens.  

Immunodeficiency: The drug should not be used in individuals with severe immunodeficiency or immunosuppression. Since drug stimulates the immune system, patients with compromised immune function may experience heightened susceptibility to infections or an increased risk of immune-related adverse events. Caution should be exercised when considering drug therapy in patients with underlying immunodeficiency disorders. 

Pregnancy and Breastfeeding:  

The safety and effectiveness of this medication for pregnant or breastfeeding individuals have not been determined. As there is a potential danger to the developing fetus or newborn, it is advised to avoid using the drug during pregnancy and while breastfeeding. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

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:  

The drug is a novel therapeutic agent with profound implications in the field of immunotherapy. It belongs to the class of adoptive cell therapies (ACTs). 

Pharmacodynamics:  

The pharmacodynamics of this drug are characterized by the activation, expansion, and persistence of CAR-T cells, resulting in targeted tumor cell elimination. Through its complex mechanism of action, drug orchestrates a multifaceted immune response, involving both direct cytotoxicity and the modulation of the tumor microenvironment. This unique therapeutic approach holds promise in the treatment of malignancies expressing the specific target antigen recognized by lifileucel CAR-T cells.   

Pharmacokinetics: 

Absorption  

The drug is administered intravenously, facilitating direct and rapid delivery into the systemic circulation. By bypassing the gastrointestinal tract, the drug avoids absorption barriers commonly encountered with oral medications.  

Distribution  

Following systemic circulation, The drug demonstrates a wide distribution throughout the body, allowing it to reach tumor sites effectively. This broad distribution can be attributed to the drug molecules’ relatively small size and ability to penetrate various tissue compartments. 

Metabolism  

Metabolism of this drug primarily occurs through intracellular processes mediated by enzymatic transformations. The drug is subject to metabolic pathways involving proteolytic cleavage, glycosylation, and phosphorylation, which can alter its structure and pharmacological properties.   

Excretion and elimination 

The elimination of this drug from the human body occurs mainly through renal excretion. The drug and its metabolites are primarily excreted via glomerular filtration and subsequent urine elimination. 

Adminstartion

Administration:  

lifleucel administration is typically preceded by a lymphodepleting chemotherapy regimen.   

This medication, administered via intravenous infusion typically in a hospital setting, aims to harness the body’s own immune system to target and combat the melanoma cells.

Patient Information Leaflet

Patient information leaflet 

Generic Name: lifileucel 

Why do we use lifileucel?   

Amtagvi (lifileucel) is utilized as a form of treatment for adults diagnosed with melanoma under specific conditions. It is employed when the melanoma is either inoperable or has spread to other parts of the body. Additionally, it is prescribed when prior treatments with PD-1 blocking drugs or BRAF inhibitors, with or without MEK inhibitors, have been ineffective or have ceased to provide benefits. This medication, administered via intravenous infusion typically in a hospital setting, aims to harness the body’s own immune system to target and combat the melanoma cells.