glofitamab

Action and Spectrum

Actions and Spectrum: 

glofitamab is a bispecific antibody designed to target both CD20 on B cells and CD3 on T cells. By binding to these two targets simultaneously, glofitamab aims to redirect T-cell activity towards malignant B cells, leading to their elimination. This mechanism of action is known as T-cell redirection. 

The action of glofitamab involves several key steps: 

• Target Binding: glofitamab binds to CD20, a protein expressed on the surface of B cells, CD3, a protein found on T cells. This dual binding allows glofitamab to bring T cells near malignant B cells. 
• T-cell Activation: Upon binding to CD3, glofitamab activates T cells, triggering their activation and release of cytotoxic granules and cytokines. This T-cell activation is crucial in initiating an immune response against B-cell malignancies. 
• B-cell Elimination: glofitamab engages CD20 on B cells, leading to the recruitment of T cells to the proximity of these malignant cells. Activated T cells then release cytotoxic granules and cytokines, inducing apoptosis (programmed cell death) of the CD20-expressing B cells. 
• Effector Functions: Besides T-cell redirection, glofitamab may also engage other effector functions of the immune system, like antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis (ADCP). These mechanisms involve activating other immune cells, such as natural killer (NK) cells and macrophages, to eliminate the targeted B cells further. 

The spectrum of glofitamab’s activity is primarily focused on B-cell malignancies that express CD20. This includes various types of non-Hodgkin lymphomas (NHL) and chronic lymphocytic leukemia (CLL). CD20 is a well-established target for B-cell malignancies, and glofitamab’s bispecific design enhances the T-cell-mediated immune response, specifically against CD20-expressing cells. 

It’s important to note that the specific spectrum of activity and clinical applications of glofitamab may be further defined and expanded through ongoing clinical trials and research. The ultimate clinical effectiveness and safety of glofitamab will depend on factors like the patient population, disease characteristics, and the specific context of use. 

Drug Interaction

Adverse Reaction

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

None 

Pregnancy / Lactation

Pregnancy consideration:  

Pregnancy category: N/A 

Lactation: Excreted into human milk is unknown 

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: 

glofitamab is a bispecific antibody designed to target both CD20 on B cells and CD3 on T cells. By binding to these two targets simultaneously, glofitamab aims to redirect T-cell activity towards malignant B cells, leading to their elimination. This mechanism of action is known as T-cell redirection. 

Here’s a general overview of the pharmacology of glofitamab: 

• Target Binding: glofitamab binds to CD20, a protein expressed on the surface of B cells, CD3, a protein found on T cells. This dual binding allows glofitamab to bring T cells near malignant B cells. 
• T-cell Activation: Upon binding to CD3, glofitamab activates T cells, triggering their activation and release of cytotoxic granules and cytokines. This T-cell activation is crucial in initiating an immune response against B-cell malignancies. 
• B-cell Elimination: glofitamab engages CD20 on B cells, leading to the recruitment of T cells to the proximity of these malignant cells. Activated T cells then release cytotoxic granules and cytokines, inducing apoptosis (programmed cell death) of the CD20-expressing B cells. 
• Effector Functions: Besides T-cell redirection, glofitamab may also engage other effector functions of the immune system, like antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis (ADCP). These mechanisms involve activating other immune cells, such as natural killer (NK) cells and macrophages, to eliminate the targeted B cells further. 

Pharmacodynamics: 

Mechanism of action: The action of this bispecific antibody is designed to work by simultaneously binding to CD3 receptors on T-cells and CD20 receptors on B-cells. This interaction leads to the activation of T-cells and triggers their ability to kill CD20+ cells selectively. CD20 is expressed on B-cells and is a well-established therapeutic target in various B-cell malignancies, such as follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. 

Pharmacokinetics: 

Pharmacokinetics (PK) studies how a drug is absorbed, distributed, metabolized, and eliminated by the body. These parameters help determine the drug’s concentration in the bloodstream, exposure to target tissues, and overall pharmacological effects. PK data assists in establishing optimal dosing regimens, understanding drug-drug interactions, and assessing the drug’s safety and efficacy. 

Some of the critical pharmacokinetic parameters assessed for therapeutic antibodies like glofitamab may include: 

Absorption:  

This parameter describes how the drug enters the bloodstream after administration. For antibodies given intravenously, absorption is not applicable as they directly enter the systemic circulation. 

Distribution: 

It relates to how the drug is distributed throughout the body. Antibodies generally have a large distribution volume, primarily in the extracellular space. 

Metabolism:  

Therapeutic antibodies are typically not metabolized to a significant extent in the body. However, some modifications may occur, such as glycosylation or proteolytic cleavage. 

Elimination:  

The clearance and half-life of the drug are essential factors in determining the duration of drug exposure in the body. Clearance represents the rate at which the drug is removed from circulation, while the half-life is the time the drug concentration takes to decrease by half. 

Adminstartion

Administration: 

Intravenous administration 

glofitamab is typically administered intravenously (IV) as an infusion. The specific administration details, including dosage, infusion duration, and schedule, may vary based on the indication and the treatment regimen recommended by healthcare professionals. It’s key to follow the instructions provided by the prescribing physician or healthcare team. 

glofitamab is slowly administered into a vein over a specified period during the infusion. The infusion rate and duration are determined based on the recommended guidelines and the patient’s tolerance to the treatment. Sometimes, a loading dose may be given initially, followed by subsequent maintenance doses. 

The healthcare provider will generally monitor the patient closely during the infusion to watch for potential adverse reactions or side effects. They may also administer pre-medications, such as antihistamines or corticosteroids, to help manage and reduce the risk of infusion-related reactions. 

It’s important to note that the administration details of glofitamab may vary, and the above information is a general overview. To obtain the precise administration instructions and guidelines for glofitamab, it is recommended to consult the prescribing information, discuss with the healthcare provider, or refer to the specific treatment protocol associated with the indication being treated. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: glofitamab 

Why do we use glofitamab? 

glofitamab (Columvi) aims to provide a targeted immunotherapeutic approach for individuals who have not achieved a satisfactory response to prior treatments or whose lymphoma has relapsed after multiple lines of therapy. By engaging both CD20 on B cells and CD3 on T cells, Columvi facilitates the redirection of T cells to recognize and eliminate CD20-expressing B cells, potentially leading to improved outcomes in these challenging cases.