mogamulizumab

Action and Spectrum

It is a humanized monoclonal antibody that targets CC chemokine receptor 4 (CCR4), a receptor expressed on certain malignant T cells, particularly in some types of T-cell lymphomas. By binding to CCR4, mogamulizumab induces antibody-dependent cellular cytotoxicity (ADCC), leading to the destruction of CCR4-expressing cancer cells. It also depletes regulatory T cells (Tregs), which may enhance the immune system’s ability to attack tumors. It is primarily used to treat cutaneous T-cell lymphoma (CTCL), including mycosis fungoides and Sezary syndrome, especially in patients who have relapsed or are refractory to other treatments. It is also approved for some cases of adult T-cell leukemia/lymphoma (ATLL). Its role is mainly in T-cell malignancies that express CCR4, offering a targeted immunotherapy option where conventional therapies may be limited. 

Drug Interaction

Adverse Reaction

Adverse drug reactions:  

Frequency defined  

>10%  

Decreased CD4 lymphocytes  

Hyperglycemia  

Decreased CD4 lymphocytes  

Rash, including drug eruption   

Anemia  

Decreased albumin  

Infusion-related reaction  

Decreased white blood cells   

Decreased lymphocytes   

Fatigue  

Decreased calcium  

Thrombocytopenia   

Uric acid increased   

Phosphate decreased   

Diarrhea  

Aspartate transaminase (AST) increased  

Drug eruption   

Upper respiratory tract infection  

Musculoskeletal pain   

Skin infection   

Constipation   

Increased calcium   

Anemia   

Mucositis   

Cough   

1-10%  

Hypertension   

Neutropenia   

Candidiasis   

Urinary tract infection   

Renal insufficiency   

Hyperglycemia   

Insomnia   

Hyperuricemia   

Increased weight   

Folliculitis   

Xerosis   

Black Box Warning

It carries a black box warning for the risk of severe and potentially life-threatening skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These serious dermatologic reactions require immediate discontinuation of the drug and prompt medical intervention.  

Contraindication / Caution

Contraindications 

Hypersensitivity 

Cautions 

Use with caution in patients with a history of severe skin reactions, as mogamulizumab can cause serious dermatologic toxicities including Stevens-Johnson syndrome and toxic epidermal necrolysis. 

Monitor closely for immune-related adverse events such as hepatitis, pneumonitis, and infusion-related reactions. 

Use cautiously in patients with pre-existing autoimmune diseases or compromised immune systems. 

Pregnancy / Lactation

Pregnancy warnings:    

• AU TGA pregnancy category: C 
• US FDA pregnancy category: not assigned 

Breastfeeding warnings: 

• The release of the drug into the human breastmilk is unknown  

Pregnancy Categories:      

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first trimester or the later trimester      
• Category B: No evidence shown of risk to the fetus found in animal reproduction studies, and there are not enough studies on pregnant women      
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for a result in humans must take care of potential risks in pregnant women      
• Category D: There is adequate data available 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 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

Mogamulizumab is a humanized monoclonal antibody that targets CCR4 on malignant and regulatory T cells, inducing their destruction through antibody-dependent cellular cytotoxicity. This boosts the immune response against tumors. It is given intravenously and used to treat T-cell cancers like cutaneous T-cell lymphoma and adult T-cell leukemia/lymphoma. 

Pharmacodynamics 

Mogamulizumab binds specifically to the CC chemokine receptor 4 (CCR4) on malignant T cells and regulatory T cells. This binding triggers antibody-dependent cellular cytotoxicity (ADCC), recruiting immune cells such as natural killer (NK) cells to destroy the CCR4-expressing target cells. Additionally, by depleting regulatory T cells, mogamulizumab reduces immune suppression, enhancing the overall anti-tumor immune response. This dual action helps to control and reduce T-cell malignancies. 

Pharmacokinetics 

Absorption: 

The peak plasma concentration of mogamulizumab is 32 mcg/mL, while the minimum plasma concentration is 11 mcg/mL.  

Distribution: 

The volume of distribution is 3.6 L. 

Metabolism: 

Metabolized through proteolytic catabolism into small peptides and amino acids, typical for monoclonal antibodies. 

Not processed by cytochrome P450 enzymes. 

Excretion and Elimination 

The rate of clearance is 12 ml/hr. 

The elimination half-life ranges approximately 17 days. 

Adminstartion

It is administered by intravenous (IV) infusion over at least 60 minutes. It should not be given as an IV push or bolus. The infusion should be prepared using a sterile, nonpyrogenic, low-protein-binding in-line filter and administered through a dedicated IV line. 

Patient Information Leaflet

Generic Name: mogamulizumab 

Pronounced: moh-GAM-yoo-LIH-zoo-mab) 

Why do we use mogamulizumab?  

It is used primarily for the treatment of certain CCR4-positive T-cell malignancies. It is approved for patients with cutaneous T-cell lymphoma (CTCL), including mycosis fungoides and Sezary syndrome, particularly in those who have relapsed or are refractory to prior treatments. Additionally, it is indicated for adult T-cell leukemia/lymphoma (ATLL) in cases where the cancer cells express CCR4. By targeting CCR4 on malignant and regulatory T cells, mogamulizumab helps reduce tumor burden and enhances immune-mediated tumor destruction.