Breyanzi

Approved Indications

Breyanzi is a personalized treatment made from a patient's own immune cells. It is used in adults to treat several types of B-cell malignancies that have relapsed (returned) or are refractory (did not respond to treatment).

Large B-cell Lymphoma (LBCL)

Breyanzi is used for adults with several subtypes of LBCL, including diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B. It may be used:

• As a second-line treatment if the cancer did not respond to initial treatment or returned within 12 months of the first treatment.
• As a third-line treatment for patients who have already received two or more other types of therapy.

Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)

Breyanzi is used for adults with CLL or SLL that has returned or failed to respond after at least two prior lines of therapy. These prior treatments must have included specific types of drugs known as BTK inhibitors and BCL-2 inhibitors.

Other Lymphomas

Breyanzi is also approved for the treatment of adults with:

• Follicular Lymphoma (FL): Used after two or more prior lines of systemic therapy.
• Mantle Cell Lymphoma (MCL): Used after at least two prior lines of therapy, including a BTK inhibitor.
• Marginal Zone Lymphoma (MZL): Used for patients with relapsed or refractory disease after previous treatments.

Breyanzi is not intended for use in patients with primary central nervous system lymphoma.

Breyanzi is a type of immunotherapy known as autologous cellular therapy. It works by reprogramming a patient's own white blood cells, specifically T cells, to identify and attack cancer. T cells are a vital part of the immune system that normally help the body fight infections.

The process of how this treatment works involves several key stages:

• Cell Collection: T cells are first collected from the patient's blood through a process similar to donating blood.
• Genetic Engineering: In a specialized laboratory, these T cells are genetically modified to produce a specific protein on their surface called a chimeric antigen receptor (CAR).
• Targeting: This new receptor is designed to recognize and bind to a protein called CD19. CD19 is found on the surface of many types of B-cell lymphoma and leukemia cells.
• Expansion and Infusion: After the modified cells are grown in large numbers, they are infused back into the patient's bloodstream.

Once inside the body, these modified T cells circulate and search for cells that have the CD19 protein. When the CAR T cells attach to these cancer cells, they activate the immune system to destroy the targeted cells. Because the treatment uses the patient's own cells, it is a highly personalized form of medicine.

Common Side Effects

Many people receiving Breyanzi experience side effects during or after treatment. Common symptoms include:

• Fatigue and extreme tiredness
• Fever and chills
• Nausea, vomiting, or diarrhea
• Headache and dizziness
• Cough or shortness of breath
• Muscle or joint pain
• Swelling in the arms or legs
• Low blood cell counts, which can lead to anemia or increased bruising

Serious Side Effects

Some side effects can be severe or life-threatening. Seek immediate medical attention if you experience any of the following:

• Cytokine Release Syndrome (CRS): This is a systemic inflammatory response. Symptoms include high fever, chills, difficulty breathing, very low blood pressure, and a fast or irregular heartbeat.
• Neurological Toxicities: These effects can impact the brain and nervous system. Symptoms include confusion, altered consciousness, seizures, difficulty speaking or understanding speech, and loss of balance.
• Severe Infections: Breyanzi can weaken the immune system, increasing the risk of developing life-threatening bacterial, viral, or fungal infections.
• Prolonged Low Blood Cell Counts: Blood counts (white cells, red cells, and platelets) may remain very low for several weeks or months following treatment.
• Secondary Malignancies: There is a potential risk of developing new types of T-cell cancers after receiving this therapy.
• Severe Allergic Reactions: Signs may include hives, rash, or swelling of the face, lips, or throat.

Boxed Warnings

Breyanzi includes boxed warnings for cytokine release syndrome and neurological toxicities, both of which can be severe or life-threatening.

Cytokine Release Syndrome (CRS)

CRS is a common and potentially serious reaction to CAR T-cell therapy. Symptoms often include high fever, chills, low blood pressure, and difficulty breathing. Healthcare providers monitor patients closely for these signs, especially in the first week after infusion.

Neurological Toxicities

Neurological side effects may occur with or without CRS. These can include confusion, tremors, dizziness, seizures, and loss of consciousness. Because of these risks, patients are advised not to drive or operate heavy machinery for at least eight weeks after treatment.

Secondary Malignancies

There is a risk of developing new cancers, such as T-cell malignancies, following treatment with Breyanzi. Healthcare providers may conduct long-term monitoring to check for any new signs of cancer.

Infections and Low Blood Counts

Breyanzi can cause serious infections and prolonged low blood cell counts (cytopenia). Low white blood cell counts can increase the risk of infection, while low platelet counts can increase the risk of bleeding. Patients may also develop low levels of antibodies, known as hypogammaglobulinemia.

Monitoring Requirements

Due to the risk of serious side effects, Breyanzi is only available through a restricted program called the Risk Evaluation and Mitigation Strategy (REMS). Patients must be monitored daily at a certified healthcare facility for at least seven days after the infusion and should stay within close proximity to the facility for at least four weeks.

Vaccinations

The use of live virus vaccines is not recommended shortly before, during, or after treatment with Breyanzi, as the safety of these vaccines has not been established in patients receiving this therapy.

Pregnancy

It is not known if Breyanzi will harm an unborn baby. There are no available data on the use of this medication in pregnant individuals, and animal reproduction studies have not been performed to evaluate its effects on fetal development. Patients should inform their healthcare provider if they are pregnant or planning to become pregnant before starting treatment to discuss potential risks and benefits.

Breastfeeding

It is unknown whether Breyanzi passes into breast milk or if it could affect a nursing child. Due to the potential for transmission of the viral vector used during the manufacturing process of this cell therapy, breastfeeding is generally not recommended. Patients should discuss infant feeding options with their healthcare team before beginning treatment.

Dosage Forms

Breyanzi is available as a suspension for intravenous infusion. It is an autologous immunotherapy, which means it is a personalized treatment manufactured specifically for each patient using their own white blood cells (T cells).

Components and Strength

The medication is supplied in vials containing two separate components that are administered together as a single treatment:

• CD8 component
• CD4 component

The strength of the dose is determined by the number of chimeric antigen receptor (CAR)-positive viable T cells. Because each dose is custom-made for the individual patient, the exact volume and cell concentration may vary within a standardized range defined by the manufacturer.

FDA Approval and Indications

Breyanzi (lisocabtagene maraleucel) was first approved by the U.S. Food and Drug Administration (FDA) in 2021. It is a chimeric antigen receptor (CAR) T-cell therapy indicated for the treatment of adults with several types of B-cell malignancies that have not responded to previous treatments or have returned after treatment. Approved indications include:

• Large B-cell lymphoma (LBCL)
• Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)
• Follicular lymphoma (FL)
• Mantle cell lymphoma (MCL)
• Marginal zone lymphoma (MZL)

Boxed Warning

The FDA has issued a Boxed Warning for Breyanzi due to the risk of serious and potentially life-threatening side effects, including:

• Cytokine Release Syndrome (CRS): A systemic inflammatory response that can cause high fever, chills, and multi-organ failure.
• Neurologic Toxicities: Serious brain and nervous system reactions, such as confusion, altered consciousness, or seizures.

Because of these risks, Breyanzi is only available through a restricted program called the Breyanzi Risk Evaluation and Mitigation Strategy (REMS). Healthcare facilities must be specially certified to administer the treatment and manage these potential complications.

Safety Communications

The FDA has issued safety communications regarding the risk of secondary T-cell malignancies following treatment with CAR T-cell therapies, including Breyanzi. While the FDA has determined that the overall benefits of these therapies continue to outweigh their potential risks for their approved uses, the agency requires manufacturers to include information about this risk in the prescribing information and continues to monitor reports of new cancers.

Factors Influencing Cost

Breyanzi is a personalized CAR-T cell therapy, which involves a complex manufacturing process using a patient's own white blood cells. Because it is a specialized, one-time treatment, the cost is typically high. Several variables determine the final amount a patient may pay:

• Insurance Coverage: Most private insurance plans, Medicare, and Medicaid may cover CAR-T cell therapy, but out-of-pocket costs such as deductibles, copayments, or coinsurance will vary by plan.
• Treatment Center: Breyanzi is only administered at certified healthcare facilities. These centers may have different billing structures for the infusion procedure and the required hospital stay.
• Associated Medical Services: The total cost often includes more than the drug itself, such as the collection of cells (leukapheresis), laboratory processing, and intensive monitoring for side effects after the treatment.

Financial Assistance

The manufacturer of Breyanzi often provides patient support services to help navigate the insurance process. These programs may offer financial assistance or cost-sharing support for eligible patients. It is recommended that patients speak with a financial counselor or social worker at their authorized treatment center to get a detailed estimate of costs and explore available support options.