elranatamab-bcmm

Action and Spectrum

Actions and Spectrum: 

elranatamab is a bispecific antibody that is engineered to target two molecules simultaneously. Specifically, it targets two proteins involved in the progression of multiple myeloma: B-cell maturation antigen (BCMA) and CD3. BCMA is highly expressed on the surface of malignant plasma cells in multiple myeloma, making it an attractive target for therapy.

CD3, on the other hand, is present on the surface of T cells, which are immune cells that play a crucial role in the body’s defense against abnormal cells. elranatamab is designed to bring T cells into proximity with BCMA-expressing myeloma cells. The antibody binds to BCMA on the myeloma cells and CD3 on the T cells. This bridging action facilitates the activation of T cells and redirects their cytotoxic activity toward the myeloma cells expressing BCMA.

elranatamab enhances the immune system’s ability to identify and destroy cancerous cells. elranatamab’s activity is specific to multiple myeloma, a type of cancer that affects plasma cells and white blood cells that produce antibodies. This antibody therapy targets BCMA, a protein highly expressed on the surface of myeloma cells. Its specificity for BCMA-expressing cells helps minimize damage to healthy cells while maximizing its impact on cancer cells. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

All Grades 

White blood cell decreased (69%) 

Neutrophil count decreased (62%) 

CRS (58%) 

Fatigue (43%) 

Creatinine increased (38%) 

Diarrhea (36%) 

Potassium decreased (36%) 

Lymphocyte count decreased (91%) 

Hemoglobin decreased (68%) 

Platelet count decreased (61%) 

Albumin decreased (55%) 

AST increased (40%) 

Injection site reaction (37% 

Grades 3 or 4 

Neutrophil count decreased (51%) 

White blood cell decreased (40%) 

Pneumonia (19%) 

Lymphocyte count decreased (84%) 

Hemoglobin decreased (43%) 

Platelet count decreased (32%) 

Sepsis (11%) 

1-10% 

All grades 

Fall (10%) 

Skin exfoliation (10%)  

Grade 3 or 4 

Potassium decreased (8%) 

Albumin decreased (6%) 

Upper respiratory tract infection (4.9%) 

Dyspnea, Grade 3 only (3.3%) 

Creatinine increased (3.3%) 

Creatinine clearance (10%) 

AST increased (6%) 

Urinary tract infection, Grade 3 only (4.4%) 

ALT increased (3.8%) 

Pyrexia, Grade 3 only (2.7%) 

Fatigue, Grade 3 only (6%) 

Black Box Warning

Black box warning: 

• Cytokine Release Syndrome (CRS): CRS is a possible adverse response to specific immunotherapies, including bispecific antibodies like elranatamab. It involves rapidly releasing cytokines into the blood, causing symptoms like fever, chills, low blood pressure, and potentially severe organ issues. The warning highlights reported life-threatening CRS reactions with elranatamab. The dosing starts gradually to minimize CRS risk. 
• Neurologic Toxicity: Neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome (ICANS), can arise due to the treatment’s impact on the immune system. ICANS leads to neurological symptoms like confusion, speech difficulties, and seizures. The warning indicates severe, life-threatening, or fatal neurologic toxicity reactions. 
• Risk Evaluation and Mitigation Strategy (REMS): Due to potential CRS and neurologic toxicity risks, Elranatamab is only accessible through a limited program called Elrexfio Risk Evaluation and Mitigation Strategy (REMS). 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

None 

Caution: 

• Cytokine Release Syndrome (CRS): May cause severe reactions like fever, low blood pressure, and organ complications. Seek medical help if CRS signs appear. 
• Neurologic Toxicity: Risk of severe nerve-related issues; monitor and care for symptoms like headaches, motor dysfunction, and sensory problems. 
• Driving and Machinery: Avoid driving or heavy machinery due to neurologic risk, especially during dosing changes. 
• Infections: Increased risk of severe infections; avoid if actively infected, monitor for signs, and treat promptly. 
• Neutropenia: Low white blood cell count risk; regularly monitor blood counts. 
• Hepatotoxicity: Possible liver toxicity; monitor liver function before and during treatment. 
• Drug Interactions: Can affect enzyme activity, impacting other drugs’ levels. Careful monitoring is needed for interactions. 

Pregnancy / Lactation

Pregnancy consideration: When given to pregnant women, the drug may cause foetal damage. 

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. 

<b>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: 

The antibody, known as elranatamab, has a unique dual-binding capability. It attaches to both CD3 receptors on T-cells and B-cell maturation antigen (BCMA) found on the surface of multiple myeloma cells. This interaction leads to the connection between T-cells and myeloma cells, triggering a solid cytotoxic T-lymphocyte response against the BCMA-presenting cells. 

Pharmacokinetics: 

Absorption 

Bioavailability: 56.2%  

Peak Plasma Time: 7 days  

Average Plasma Concentration: 

• First full 76-mg dose: 3.1 mcg/mL 
• End of weekly dose (week 24): 32.7 mcg/mL 
• Steady-state (biweekly dosing): 18.4 mcg/mL 

Maximum Plasma Concentration: 

• First full 76-mg dose: 3.8 mcg/mL 
• End of weekly dose (week 24): 33.6 mcg/mL 
• Steady-state (biweekly dosing): 20.1 mcg/mL 

Trough Plasma Concentration: 

• First full 76-mg dose: 3.3 mcg/mL 
• End of weekly dose (week 24): 31.2 mcg/mL 
• Steady-state (biweekly dosing): 15.9 mcg/mL 

Distribution 

• Vd (Volume of distribution): 7.76 L  

Metabolism 

The drug is metabolized into small peptides by catabolic pathways. 

Elimination and Excretion 

• Half-life: 22 days (76-mg dose)  
• Clearance: 0.324 L/day (after 24 weeks) 

Adminstartion

Administration: 

Subcutaneous administration 

Inject into the abdominal subcutaneous tissue (recommended injection location).  

Never administer an injection to skin that is red, bruised, painful, complex, or not intact, as well as into regions with scars or tattoos. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: elranatamab-bcmm 

Why do we use elranatamab-bcmm? 

elranatamab (formerly known as AMG 420) is an investigational drug designed to treat multiple myeloma, a type of cancer affecting plasma cells in the bone marrow. It falls into the category of immunotherapies, specifically bispecific T-cell engager (BiTE) antibodies.

These drugs are engineered to engage cancer cells and T-cells of the immune system, helping the immune system recognize and target cancer cells more effectively.