Gazyva

Chronic Lymphocytic Leukemia

Gazyva is used to treat chronic lymphocytic leukemia (CLL) in adults who have not received previous treatment for the condition. For this indication, it is typically prescribed in combination with a chemotherapy drug called chlorambucil.

Follicular Lymphoma

Gazyva is also used to treat follicular lymphoma (FL), which is a type of non-Hodgkin lymphoma, in two specific situations:

• Previously untreated: It is used for adults with Stage II bulky, Stage III, or Stage IV follicular lymphoma who have not yet been treated. In this case, it is initially given with chemotherapy and then continued as a single-agent treatment.
• Relapsed or refractory: It is used for adults whose follicular lymphoma returned or did not improve after previous treatment with a regimen containing rituximab. For this use, it is given with a chemotherapy drug called bendamustine and then continued as a single-agent treatment.

Mechanism of Action

Gazyva belongs to a class of medications known as monoclonal antibodies. It is specifically designed to recognize and attach to a protein called CD20, which is found on the surface of B-cells. B-cells are a type of white blood cell that can become cancerous in conditions such as chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL).

When Gazyva attaches to the CD20 protein on these abnormal cells, it works in several ways to combat the cancer:

• Immune System Recruitment: The medication acts as a flag, signaling the body's own immune system to identify, attack, and kill the cancerous B-cells.
• Direct Cell Death: Gazyva can cause the cancerous cells to self-destruct directly upon attachment.
• Cellular Destruction: It helps other specialized immune cells release substances that destroy the targeted cancer cells.

By targeting and reducing the number of these abnormal B-cells, Gazyva helps to slow or stop the progression of the disease. Because CD20 is also found on some healthy B-cells, the medication may also affect normal B-cells, though the body can typically produce new, healthy ones after treatment.

Common Side Effects

• Fever and chills
• Tiredness or weakness
• Nausea, diarrhea, or constipation
• Cough
• Headache
• Muscle or joint pain
• Hair loss
• Skin rash

Serious Side Effects

• Severe infusion reactions, which may include chest pain, dizziness, or difficulty breathing
• Low white blood cell, red blood cell, or platelet counts
• Tumor Lysis Syndrome, a condition caused by the rapid breakdown of cancer cells that can affect the kidneys
• Reactivation of Hepatitis B in people who have previously carried the virus
• Progressive Multifocal Leukoencephalopathy (PML), a rare and serious brain infection
• Severe infections, such as pneumonia or urinary tract infections

Patients should seek medical attention immediately if they experience signs of an allergic reaction, unusual bruising or bleeding, or persistent fever.

Boxed Warnings

Gazyva has boxed warnings for the following serious conditions:

• Hepatitis B Reactivation: The hepatitis B virus (HBV) may become active again in people who have had the virus in the past. This can lead to severe liver damage, liver failure, or death. Healthcare providers typically screen for HBV before starting treatment.
• Progressive Multifocal Leukoencephalopathy (PML): This is a rare but life-threatening brain infection caused by a virus. Symptoms may include confusion, dizziness, loss of balance, difficulty walking or talking, and vision changes.

Infusion-Related Reactions

Severe and life-threatening reactions can occur during or shortly after the infusion, especially during the first dose. Monitoring is necessary for symptoms such as:

• Fever or chills
• Nausea or vomiting
• Dizziness or lightheadedness
• Rapid heartbeat
• Shortness of breath or wheezing

Tumor Lysis Syndrome (TLS)

TLS occurs when cancer cells break down quickly, releasing their contents into the bloodstream. This can cause kidney failure and abnormal heart rhythms. Preventive measures often include hydration and specific medications to lower uric acid levels before treatment begins.

Infections and Blood Counts

Treatment can increase the risk of serious bacterial, fungal, or viral infections. It may also cause a significant drop in white blood cells (neutropenia) and platelets (thrombocytopenia), which increases the risk of infection and bleeding. These counts are typically monitored throughout treatment.

Vaccinations

Live vaccines should not be administered during treatment or until the immune system has recovered. The safety and effectiveness of vaccines given during or after Gazyva treatment have not been fully established.

Pregnancy

Gazyva can cause harm to a fetus when administered to a pregnant person. Healthcare providers typically recommend avoiding pregnancy while undergoing treatment with this medication.

Key considerations for pregnancy include:

• Contraception: Individuals who can become pregnant should use effective birth control during treatment and for at least 6 months after the final dose of Gazyva.
• Testing: A pregnancy test may be required before starting this medication to confirm that the patient is not pregnant.
• Exposure: If pregnancy occurs during treatment or shortly after, it is important to contact a healthcare provider immediately to discuss potential risks to the fetus.

Breastfeeding

It is not known if Gazyva passes into breast milk or how it might affect a nursing infant. Because of the potential for serious adverse reactions, breastfeeding is generally not recommended during treatment and for at least 6 months after the last dose. Patients should discuss feeding options with their medical team.

Administration Form

Gazyva is provided as a sterile, preservative-free liquid solution in a single-dose vial. It is a concentrated medication that must be diluted by a healthcare professional before it is used.

The medication is administered as an intravenous infusion, meaning it is delivered directly into a vein over a period of time. It is not available in oral forms such as tablets or capsules.

FDA Approval and Indications

Gazyva was first approved by the U.S. Food and Drug Administration (FDA) in November 2013. It is currently approved for the following indications:

• Chronic Lymphocytic Leukemia (CLL): Used in combination with chlorambucil for patients who have not been previously treated.
• Follicular Lymphoma (FL): Used in combination with bendamustine for patients whose cancer returned or did not respond to a previous treatment regimen that included rituximab.
• Untreated Follicular Lymphoma: Used in combination with chemotherapy, followed by Gazyva monotherapy, for patients with previously untreated Stage II bulky, III, or IV follicular lymphoma.

Boxed Warnings

The FDA has issued a boxed warning for Gazyva due to the risk of two serious conditions:

• Hepatitis B Virus (HBV) Reactivation: In patients who have previously had hepatitis B, the virus can become active again during or after treatment with Gazyva. This reactivation can lead to severe liver damage, liver failure, or death. Healthcare providers typically screen for HBV infection before starting treatment.
• Progressive Multifocal Leukoencephalopathy (PML): This is a rare but serious brain infection caused by a virus. It can lead to severe disability or death. Patients are monitored for any new or worsening neurological symptoms while receiving this medication.

Factors Affecting Cost

Gazyva is a brand-name biologic medication. The total cost of treatment can vary significantly based on several factors:

• Insurance coverage: Your out-of-pocket costs will depend on whether your insurance plan covers the drug and what your specific copay or coinsurance requirements are.
• Treatment schedule: The number of doses and the length of your treatment course will affect the overall price.
• Administration fees: Because Gazyva is given as an intravenous infusion in a medical setting, you will likely face costs for the facility and the healthcare professionals who administer the drug.

Biosimilar Availability

There are currently no biosimilar versions of Gazyva. Biologics like Gazyva are made from living cells, making them more complex and expensive to produce than standard chemical drugs. Without a biosimilar alternative, the price of the brand-name drug typically remains high.

Financial Assistance

The manufacturer offers support services to help patients navigate the cost of Gazyva. This may include copay assistance for those with commercial insurance or patient assistance programs for individuals who meet certain financial criteria or lack insurance coverage. You can speak with your healthcare provider or a financial counselor at your treatment center to explore these options.