belantamab mafodotin

Action and Spectrum

Actions and Spectrum: 

Mechanism of Action: 

• Binding to BCMA: belantamab mafodotin is an antibody-drug conjugate that consists of an anti-B-cell maturation antigen (BCMA) monoclonal antibody linked to a cytotoxic agent, monomethyl auristatin F (MMAF). BCMA is a protein highly expressed on multiple myeloma cells’ surfaces. 
• Internalization and release of MMAF: belantamab mafodotin binds specifically to BCMA on the surface of multiple myeloma cells. After binding, the complex is internalized by the cells through receptor-mediated endocytosis. This internalization process allows the release of the cytotoxic MMAF into the cancer cells. 
• Cell killing by MMAF: When cancer cells release MMAF, it links to tubulin, a protein that helps cells divide. MMAF breaks up the microtubule network, which stops the multiple myeloma cells from dividing and makes them die by apoptosis (programmed cell death).

Spectrum of Activity:  

• Patients with relapsed or refractory multiple myeloma who have previously been treated with at least four treatments, including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 monoclonal antibody, may benefit from therapy with belantamab mafodotin. 
• Its activity is primarily directed toward multiple myeloma cells that express BCMA, a distinguishing characteristic of this type of cancer. BCMA expression is typically high on the surface of multiple myeloma cells, making them susceptible to the targeted action of belantamab mafodotin. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

All grades 

Platelets decreased (62%) 

Decreased visual acuity (53%) 

Albumin decreased (43%) 

Hemoglobin decreased (32%) 

Neutrophils decreased (28%) 

Gamma-glutamyl transferase increased (25%) 

Blurred vision (22%) 

Keratopathy (71%) 

AST increased (57%) 

Lymphocytes decreased (49%) 

Glucose increased (38%) 

Creatinine increased (28%) 

Alkaline phosphatase increased (26%) 

Nausea (24%) 

Creatinine phosphokinase increased (22%) 

Infusion-related reactions (21%) 

Potassium decreased (20%) 

Dry eyes (14%) 

Diarrhea (13%) 

Decreased appetite (12%) 

Upper respiratory tract infection (11%) 

Pyrexia (22%) 

Sodium decreased (21%) 

Fatigue (20%) 

Constipation (13%) 

Arthralgia (12%) 

Back pain (11%)  

Grade 3-4 

Decreased visual acuity (28%) 

Platelets decreased (21%) 

Keratopathy (44%) 

Lymphocytes decreased (22%) 

Hemoglobin decreased (18%)  

1-10% 

All grades 

Eye irritation (<10%) 

Ulcerative keratitis (<10%) 

Pneumonia (<10%) 

Photophobia (<10%) 

Infective keratitis (<10%) 

Vomiting (<10%) 

Albuminuria (<10%)  

Grade 3-4 

Creatinine increased (5%) 

Blurred vision (4%) 

Infusion-related reactions (3%) 

Glucose increased (3%) 

Neutrophils decreased (9%) 

Gamma-glutamyl transferase increased (5%) 

Albumin decreased (4%) 

Pyrexia (3%) 

AST increased (2%) 

Post-marketing reports 

Pneumonitis 

Black Box Warning

Black box warning: 

The black box warning for belantamab mafodotin highlights the risk of ocular toxicity, specifically corneal epithelial changes, and changes in visual acuity. 

• Ocular toxicity: belantamab mafodotin can cause severe and sometimes irreversible ocular toxicity. The most common ocular adverse events associated with belantamab mafodotin include changes in the corneal epithelium (corneal epithelial microcysts, punctate keratitis, and decreased corneal sensitivity), blurred vision, dry eyes, and eye pain. 
• Keratopathy: belantamab mafodotin treatment can lead to a condition called keratopathy, characterized by changes in the cornea. These changes can include epithelial microcysts, corneal edema, corneal erosions, and ulcerations. Keratopathy may result in visual disturbances, potentially leading to severe complications such as corneal perforation or blindness. 
• Monitoring and Management: Monitoring patients receiving belantamab mafodotin for ocular toxicity is crucial. Before starting treatment, a comprehensive ophthalmic examination should be performed, including an assessment of visual acuity, slit-lamp examination, and measurement of corneal sensitivity. Regular monitoring of visual symptoms, visual acuity, and corneal examinations should be conducted during treatment. If ocular toxicity is detected, appropriate management strategies may be required, such as dose modification, treatment interruption, or discontinuation. 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

None 

Caution: 

• Ocular toxicity: belantamab mafodotin is associated with ocular toxicity, including corneal epithelial changes and changes in visual acuity. Patients should be monitored closely for ocular symptoms and undergo regular ophthalmic examinations during treatment. 
• Infusion-Related Reactions: Infusion-related reactions, such as fever, chills, nausea, headache, and dyspnea, have been reported with belantamab mafodotin. Patients should be closely monitored during the infusion, and appropriate supportive care measures should be taken as needed. If severe infusion-related reactions occur, the infusion may need to be interrupted or discontinued. 
• Hematologic toxicity: belantamab mafodotin may cause hematologic toxicities, including neutropenia, thrombocytopenia, and anemia. Regular monitoring of blood counts is recommended during treatment. Depending on the severity of hematologic toxicities, dose modifications or treatment interruptions may be necessary. 
• Hepatotoxicity: Liver function abnormalities, including increased liver enzymes, have been observed with belantamab mafodotin treatment. Regular monitoring of liver function tests is required, with corrective action conducted in the event of hepatotoxicity. 
• Embryo-Fetal toxicity: belantamab mafodotin can cause fetal harm if administered during pregnancy. It is advised to use effective contraception during treatment and at least five months after the last dose of belantamab mafodotin. 
• Use in Specific Populations: The safety and efficacy of belantamab mafodotin have not been established in pediatric patients, and its use in this population is not recommended. There is little evidence on the use of belantamab mafodotin in individuals with moderate to severe renal or hepatic impairment. When treating individuals with these illnesses, extreme caution should be used, and dosage changes may be required. 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast 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: 

belantamab mafodotin (Blenrep) is an antibody-drug conjugate (ADC) used to treat multiple myeloma. Its pharmacology targets B-cell maturation antigen (BCMA) expressed on multiple myeloma cells. 

• Target Specificity: belantama mafodotin targets B-cell maturation antigen (BCMA), which is highly expressed on the surface of multiple myeloma cells. BCMA is involved in the survival and growth of malignant plasma cells. 
• Antibody Binding: The monoclonal antibody component of belantamab mafodotin binds specifically to BCMA, facilitating the selective targeting of multiple myeloma cells. 
• Internalization and Drug Release: Once bound to BCMA, belantamab mafodotin is internalized into the multiple myeloma cells through receptor-mediated endocytosis. Inside the cell, the cytotoxic agent, monomethyl auristatin F (MMAF), is released from the antibody-drug conjugate. 
• Cytotoxic Effect: MMAF exerts its cytotoxic effect by binding to tubulin, a protein involved in microtubule assembly, disrupting the microtubule network and inhibiting cell division. This ultimately induces apoptosis (programmed cell death) in the targeted multiple myeloma cells. 

Pharmacodynamics: 

• Binding to BCMA: belantamab mafodotin is an antibody-drug conjugate (ADC) composed of an anti-BCMA monoclonal antibody linked to a cytotoxic agent called monomethyl auristatin F (MMAF). The monoclonal antibody component of the ADC specifically recognizes and binds to BCMA on the surface of myeloma cells. 
• Internalization and release of MMAF: Once belantamab mafodotin binds to BCMA, the myeloma cells internalize the ADC through receptor-mediated endocytosis. Once inside the cells, the cytotoxic agent MMAF is released from the ADC. 
• Cytotoxic effect: MMAF is a potent microtubule-disrupting agent that inhibits cell division and induces apoptosis (programmed cell death) in the myeloma cells. It binds to tubulin, a protein involved in the formation of microtubules, disrupting the microtubule network and inhibiting cell division. 
• Anti-tumor activity: By specifically targeting BCMA-expressing myeloma cells and delivering the cytotoxic agent MMAF, belantamab mafodotin induces cell death and reduces the growth of myeloma tumors. 

Pharmacokinetics: 

Absorption 

belantamab mafodotin is administered intravenously, allowing rapid and complete absorption of the medication into the bloodstream. As an intravenous formulation, the drug bypasses the typical absorption phase of oral medications. 

Distribution 

Once in the bloodstream, belantamab mafodotin is distributed throughout the body. It binds specifically to BCMA-expressing cells, including multiple myeloma cells and normal BCMA-expressing tissues. 

Metabolism 

belantamab mafodotin undergoes metabolic processes in the body. The cytotoxic agent MMAF, released from the ADC, is metabolized primarily by non-specific intracellular enzymes. The specific metabolic pathways and enzymes involved in the metabolism of MMAF have not been extensively characterized. 

Elimination and Excretion 

The elimination of belantamab mafodotin and its metabolites primarily occurs through renal excretion. After metabolism of MMAF, the resulting metabolites are eliminated from the body through the urine. 

Adminstartion

Administration: 

The general guidelines for the administration of belantamab mafodotin: 

• Pre-medication: Before receiving belantamab mafodotin, patients may be given pre-medications to help manage potential infusion-related reactions, such as antihistamines and corticosteroids. The pre-medication regimen may vary based on individual patient needs and the healthcare provider’s discretion. 
• Dosing schedule: belantamab mafodotin is typically administered once every three weeks (every 21 days) as a 30-minute intravenous infusion. The healthcare provider should determine the exact dosage and treatment schedule based on the patient’s condition, response to treatment, and any potential dose modifications or interruptions that may be needed. 
• Infusion process: The belantamab mafodotin infusion is prepared by diluting the medication in an appropriate volume of sterile saline solution. The infusion is administered through a vein in the arm or hand using an intravenous line. The healthcare provider will closely monitor the patient during the infusion for any signs of infusion-related reactions or other adverse effects. 
• Ophthalmologic monitoring: Due to the potential ocular toxicities associated with belantamab mafodotin, regular ophthalmologic monitoring is recommended. This may include visual acuity assessments, eye exams, and monitoring for ocular symptoms such as changes in vision or eye discomfort. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: belantamab mafodotin 

Why do we use belantamab mafodotin? 

• belantamab mafodotin is primarily used to treat multiple myeloma, a type of cancer affecting plasma cells in the bone marrow. It is specifically indicated for use in patients who have received at least four prior therapies, including an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody. 
• The primary use of belantamab mafodotin is as a targeted therapy against B-cell maturation antigen (BCMA), a protein found on the surface of myeloma cells. By explicitly targeting BCMA-expressing cells, belantamab mafodotin helps inhibit the growth and survival of myeloma cells. 
• belantamab mafodotin is used as a single-agent therapy administered as a standalone treatment. It is typically prescribed when other treatment options have been exhausted or have not provided adequate results. Treatment with belantamab mafodotin aims to achieve disease control, reduce the progression of multiple myeloma, and improve patient outcomes.