Relatlimab

Approved Uses

Relatlimab is used to treat a type of skin cancer called melanoma in adults and children 12 years of age and older. It is specifically prescribed for melanoma that:

• Has spread to other parts of the body (metastatic).
• Cannot be removed by surgery (unresectable).

Relatlimab is not used as a standalone treatment. It is administered in a fixed-dose combination with another immunotherapy medication called nivolumab. This combination is designed to help the immune system identify and attack melanoma cells more effectively.

Immune Checkpoint Inhibition

Relatlimab is a type of monoclonal antibody known as an immune checkpoint inhibitor. The immune system naturally uses checkpoints to keep immune responses under control and prevent the body from attacking its own healthy cells. However, some cancer cells can exploit these checkpoints to hide from the immune system.

Targeting LAG-3

Relatlimab specifically targets a protein called lymphocyte-activation gene 3 (LAG-3). This protein is found on the surface of T cells, which are white blood cells responsible for fighting diseases and tumors. When LAG-3 is activated, it acts like a brake, slowing down or stopping the T cells from attacking.

By binding to and blocking the LAG-3 protein, relatlimab helps to:

• Release the brakes on the immune system.
• Reactivate T cells that have become exhausted or inactive.
• Allow the immune system to better identify and destroy melanoma cells.

Combination Therapy

Relatlimab is used in combination with nivolumab, another checkpoint inhibitor that targets a different protein called PD-1. Because these two drugs block different pathways that cancer cells use to evade the immune system, using them together may help the immune system fight the cancer more effectively than using one drug alone.

Common Side Effects

The most common side effects reported by people taking relatlimab in combination with nivolumab include:

• Fatigue and tiredness
• Musculoskeletal pain, including joint and muscle aches
• Skin rash and itching
• Diarrhea
• Nausea
• Headache
• Decreased appetite
• Cough
• Constipation
• Vitiligo (loss of skin pigment)

Serious Side Effects

Relatlimab can cause the immune system to attack healthy parts of the body. These immune-mediated side effects can occur in any organ and may become serious or life-threatening. Seek medical help immediately for symptoms such as:

• Lung problems: New or worsening cough, shortness of breath, or chest pain.
• Intestinal problems: Severe stomach pain, diarrhea, or stools that are black, tarry, or contain blood or mucus.
• Liver problems: Yellowing of the skin or eyes, dark urine, or pain on the right side of the stomach area.
• Hormone problems: Headaches that will not go away, extreme tiredness, weight changes, increased thirst, or mood changes.
• Kidney problems: Decrease in urine output, blood in the urine, or swelling in the ankles.
• Heart problems: Chest pain, shortness of breath, or a racing or irregular heartbeat.
• Skin problems: Severe rash, blistering, or peeling skin.

Infusion reactions can also occur during the administration of the drug. Symptoms may include chills, dizziness, fever, or wheezing. Healthcare providers typically monitor patients closely during and after the infusion.

Immune-Mediated Adverse Reactions

Relatlimab can cause the immune system to attack various parts of the body. These reactions can happen at any time during or after treatment and may affect several organs simultaneously. Serious or fatal reactions have been reported in the following areas:

• Lungs: Inflammation of the lungs (pneumonitis) can cause shortness of breath, cough, or chest pain.
• Intestines: Inflammation of the colon (colitis) may lead to diarrhea, severe stomach pain, or blood in the stool.
• Liver: Inflammation of the liver (hepatitis) can cause yellowing of the skin or eyes (jaundice), dark urine, or pain on the right side of the stomach area.
• Hormone Glands: The medication can affect the thyroid, pituitary, and adrenal glands, as well as the pancreas (Type 1 diabetes). Symptoms may include extreme tiredness, weight changes, or increased thirst and urination.
• Kidneys: Inflammation of the kidneys (nephritis) can lead to changes in the amount or color of urine or swelling in the ankles.
• Skin: Severe rashes, itching, or blistering may occur.

Infusion Reactions

Some patients may experience reactions while the medication is being infused into a vein. Symptoms can include chills, shaking, itching, rash, flushing, shortness of breath, or dizziness. Healthcare providers typically monitor patients during the infusion to manage these symptoms immediately.

Stem Cell Transplant Risks

Complications can occur in patients who receive a stem cell transplant using donor cells (allogeneic) before or after treatment with this medication. These complications can be severe and require close medical supervision to monitor for signs of graft-versus-host disease.

Pregnancy and Breastfeeding

Relatlimab may cause harm to an unborn baby. Individuals who can become pregnant are usually advised to use effective birth control during treatment and for at least five months after the last dose. Breastfeeding is generally not recommended during treatment and for five months following the final dose due to potential risks to the infant.

Monitoring

Regular blood tests and physical exams are necessary to check liver function, hormone levels, and kidney function. Early detection of side effects is critical for managing immune-mediated reactions, which may require stopping the medication or starting corticosteroid treatment.

Pregnancy

Relatlimab can cause serious harm to an unborn baby. Healthcare providers typically perform a pregnancy test before starting treatment to ensure a patient is not pregnant. If you are pregnant or planning to become pregnant, discuss the potential risks with your healthcare team.

Patients who can become pregnant should use effective birth control during treatment and for at least 5 months after the final dose. If pregnancy occurs during treatment, notify a doctor right away.

Breastfeeding

It is not known if relatlimab passes into breast milk. Because of the risk of serious side effects in a nursing infant, breastfeeding is not recommended during treatment and for at least 5 months after the last dose.

Available Forms

Relatlimab is administered as an injection into a vein by a healthcare professional. It is provided as a liquid solution in a vial.

This medication is currently available only as a fixed-dose combination with nivolumab. It is not available as a standalone product.

• Intravenous solution

FDA Approval Status

The U.S. Food and Drug Administration (FDA) approved relatlimab in March 2022. It is currently approved only as a fixed-dose combination with nivolumab, administered as an intravenous infusion.

Approved Indications

This combination treatment is indicated for adult and pediatric patients 12 years of age or older with the following conditions:

• Unresectable melanoma: Skin cancer that cannot be removed by surgery.
• Metastatic melanoma: Skin cancer that has spread to other parts of the body.

Regulatory Background

The approval was based on clinical trial data demonstrating that the combination of relatlimab and nivolumab improved progression-free survival compared to nivolumab alone. Relatlimab is the first LAG-3 blocking antibody to receive FDA approval. While the medication carries risks for serious immune-related adverse reactions, there are currently no boxed warnings or Risk Evaluation and Mitigation Strategies (REMS) specifically mandated for this product beyond standard clinical monitoring.

FDA Approval Overview

The U.S. Food and Drug Administration (FDA) approved relatlimab in March 2022. It is approved for use only as a fixed-dose combination with another immunotherapy drug, nivolumab. This combination is marketed under the brand name Opdualag.

Approved Indications

The FDA has approved the combination of relatlimab and nivolumab for the treatment of:

• Adults with unresectable or metastatic melanoma.
• Pediatric patients 12 years of age and older who weigh at least 40 kilograms (about 88 pounds) with unresectable or metastatic melanoma.

Unresectable melanoma is skin cancer that cannot be removed through surgery. Metastatic melanoma is cancer that has spread from the skin to other parts of the body.

Drug Class Significance

Relatlimab is the first drug in a class called LAG-3 blocking antibodies to receive FDA approval. It works by blocking a protein called LAG-3 on immune cells, which helps the immune system more effectively attack melanoma cells.