nivolumab and relatlimab

Action and Spectrum

Actions and spectrum: 

nivolumab: 

• Action: nivolumab is a monoclonal antibody that targets the programmed cell death protein 1 receptor, allowing them to recognize and attack cancer cells. 
• Spectrum: nivolumab is approved for the treatment of several types of cancers like non-small cell lung cancer, melanoma, renal cell carcinoma, Hodgkin lymphoma, and others. 

relatlimab: 

• Action: relatlimab is a monoclonal antibody that targets the lymphocyte activation gene 3 (LAG-3) protein, which is involved in regulating immune responses. 
• Spectrum: relatlimab is primarily being investigated for the treatment of solid tumors, including advanced melanoma, lung cancer, and various gastrointestinal malignancies. It is used in combination with other immunotherapeutic agents, such as nivolumab, to enhance anti-cancer immune responses. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

Grade 3-4 

• Musculoskeletal pain (4.2%) 
• Decreased hemoglobin (2.7%) 
• Increased AST (2.3%) 
• Diarrhea (2%) 
• Decreased sodium (1.2%) 
• Increased ALT (3.2%) 
• Decreased lymphocytes (2.5%) 
• Fatigue (2%) 
• Rash (1.4%)

>10% 

All grades 

• Fatigue (39%) 
• Decreased lymphocytes (32%) 
• Rash (28%) 
• Pruritus (25%) 
• Decreased sodium (24%) 
• Increased creatinine (19%) 
• Nausea (17%) 
• Decreased appetite (15%) 
• Vitiligo (<15%) 
• Myocarditis (<15%) 
• Musculoskeletal pain (45%) 
• Decreased hemoglobin (37%) 
• Increased AST (30%) 
• Increased ALT (26%) 
• Diarrhea (24%) 
• Increased alkaline phosphatase (19%) 
• Headache (18%) 
• Hypothyroidism (17%) 
• Cough (15%) 
• Adrenal sufficiency (<15%) 
• Hepatitis (<15%) 

<1% 

Grade 3-4 

• Decreased appetite (0.6%) 
• Headache (0.3%) 
• Nausea (0.6%) 
• Increased alkaline phosphatase (0.6%) 
• Cough (0.3%) 

Black Box Warning

Black Box Warning: 

nivolumab and relatlimab have black box warnings regarding the risk of immune-mediated adverse reactions, including severe or fatal immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and dermatologic reactions.

They may also increase the risk of embryo-fetal toxicity. Close monitoring and prompt management of adverse events are essential during treatment with these medications. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: These drugs should not be used in individuals with a known hypersensitivity or severe allergic reaction to nivolumab, relatlimab, or any of their components. 

Caution: 

• Immune-related adverse reactions: These drugs can cause immune-mediated adverse reactions, which may affect multiple organs and systems. 
• Infusion-related reactions: Infusion-related reactions, including hypersensitivity reactions, may occur during or after administration of nivolumab and relatlimab.  
• Immunosuppression: nivolumab and relatlimab can lead to immune suppression, increasing the risk of infections.  
• Hepatotoxicity: These drugs can cause hepatotoxicity, including liver function test abnormalities and liver injury.  
• Endocrine disorders: nivolumab and relatlimab can cause immune-related endocrine disorders, such as thyroid dysfunction, adrenal insufficiency, and type 1 diabetes mellitus.

Comorbidities: 

• Autoimmune disorders: Patients with pre-existing autoimmune disorders like rheumatoid arthritis, lupus, or inflammatory bowel disease, may be at an increased risk of immune-related adverse events when treated with nivolumab and relatlimab. Close monitoring is required, and caution should be exercised in these patients. 
• Organ dysfunction: Patients with underlying liver, kidney, or lung dysfunction may require dosage adjustments or closer monitoring when receiving nivolumab and relatlimab. The impact of these medications on organ function and any potential exacerbation of existing conditions should be carefully assessed. 
• Infections: Patients with active infections or a history of recurrent infections may be at an increased risk of developing infections during treatment with nivolumab and relatlimab. Close monitoring for signs of infection and appropriate management strategies are essential. 
• Cardiovascular disease: Patients with a history of cardiovascular disease, including myocardial infarction, heart failure, or arrhythmias, may require additional monitoring during treatment with nivolumab and relatlimab due to the potential risk of cardiovascular events. 
• Metabolic disorders: Patients with pre-existing metabolic disorders, such as diabetes or hyperlipidemia, may require close monitoring and management of their conditions during treatment with nivolumab and relatlimab. 

Pregnancy / Lactation

Pregnancy consideration: N/A 

Lactation: N/A 

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: 

nivolumab targets the programmed death receptor-1 (PD-1) on immune cells, which inhibits the activity of T cells. By blocking PD-1, nivolumab allows T cells to recognize and attack cancer cells. 

relatlimab targets the lymphocyte-activation gene 3 (LAG-3) protein, which is expressed on activated T cells and regulatory T cells. By blocking LAG-3, relatlimab helps to enhance the anti-tumor immune response. 

Both nivolumab and relatlimab have similar mechanisms of action, aiming to unleash the body’s immune response against cancer cells by modulating immune checkpoints. Their use as monotherapy or in combination regimens has shown promising results in improving clinical outcomes for patients with various types of cancer.  

Pharmacodynamics: 

nivolumab promotes T cell-mediated cytotoxicity, cytokine production, and tumor cell killing. It also helps to restore the anti-tumor immune response by disrupting the tumor’s ability to evade immune surveillance. 

relatlimab enhances T cell activation, proliferation, and effector functions. It helps to overcome immune tolerance mechanisms and promotes anti-tumor immune responses. 

The pharmacodynamic effects of nivolumab and relatlimab include improved T cell activity, cytokine release, and inhibition of tumor immune evasion mechanisms. These pharmacodynamic properties contribute to their efficacy in the treatment of various cancers.  

Pharmacokinetics: 

Absorption 

nivolumab/relatlimab is administered intravenously, resulting in rapid and complete systemic exposure. 

Distribution 

It has a large volume of distribution, indicating extensive distribution in the body tissues. 

Metabolism 

nivolumab/relatlimab is not metabolized by cytochrome P450 enzymes or other metabolic pathways. 

Excretion 

The primary route of elimination for nivolumab/relatlimab is through the reticuloendothelial system and clearance by the immune system. 

Adminstartion

Administration: 

nivolumab and relatlimab are both administered intravenously. The exact administration protocol may vary depending on the specific indication and the healthcare provider’s instructions. Typically, these medications are administered by healthcare professionals in a clinic or hospital setting. 

The dosing and administration schedule for nivolumab and relatlimab will be determined by the healthcare provider based on factors such as the patient’s weight, medical condition, and treatment goals. The medications are infused into a vein over a specified time period, typically ranging from 30 minutes to several hours. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: nivolumab and relatlimab 

Pronounced: (nye-VOH-luh-mab-and- ruh-LAT-li-mab)  

Why do we use nivolumab and relatlimab? 

This combination drug belongs to a category of drugs referred to as monoclonal antibodies. nivolumab and relatlimab are prescribed for individuals aged 12 and above, with a minimum weight of 88 lbs (40 kg), who are dealing with a form of skin cancer known as melanoma that has either spread or is not amenable to surgical removal.

• Melanoma: nivolumab is used as a first-line treatment for advanced melanoma and as an adjuvant treatment after surgical removal of melanoma. 
• Non-Small Cell Lung Cancer (NSCLC): nivolumab is used as a second-line or subsequent treatment for metastatic NSCLC. 
• Renal Cell Carcinoma (RCC): nivolumab is used as a second-line or subsequent treatment for advanced RCC. 
• Hodgkin Lymphoma: nivolumab is used as a salvage therapy for relapsed or refractory Hodgkin lymphoma. 
• Head and Neck Cancer: nivolumab is used as a second-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck. 
• Solid Tumors: relatlimab is being investigated for its potential use in various solid tumors as part of combination therapies.