Expanding Access For Patients, Safety Restrictions Lifted For CAR T-Cell Therapy Breyanzi—A Powerful Treatment ForDiffuse Large B-Cell Lymphoma (DLBCL)

The FDA is saying these therapies are more widely understood now, allowing medical facilities to decipher whether they are able to manage the complex administration process and side effects.

The government stated in their announcement, “FDA expects that the REMS elimination, and these labeling updates, will help improve access to these products, particularly for patients who live in rural areas, while ensuring safe and effective administration to patients who need them.”

This change in safety requirements comes just four years after Breyanzi was approved for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after more than two lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL).

This drug was approved in 2021 for third-line use and cleared by the FDA in 2024 for certain second-line patients — including those too frail for stem-cell transplant.​

The treatment shows high response (≈ 70 % overall; 50% complete) with lower rates of severe toxicity compared to earlier products.

Breyanzi is FDA-approved for four B‑cell blood cancers in adults, with full approval for LBCL, and accelerated approval for CLL/SLL, Follicular, and Mantle cell lymphoma.

Revolutionizing Lymphoma Treatment: How CAR T-Cell Therapy is Transforming Outcomes in Diffuse Large B-Cell Lymphoma

CAR T-cell therapy —an approach that re-engineers a patient’s own immune cells to hunt down lymphoma, and a number of other types of blood cancer— has changed the treatment landscape, offering many people a chance at durable remission when other treatments have failed.

Dr. Manali Kamdar, associate professor and the clinical director of lymphoma services at the University of Colorado, previously told SurvivorNet that before CAR T-cell therapy, or chimeric antigen receptor T-cell therapy, patients would often relapse after treatment with a chemotherapy combination.

“I would say prior to the advent of CAR T-cell therapy in patients with diffuse large B-cell lymphoma, our first shot was our best shot, with rituximab plus chemotherapy as an option like R-CHOP or R-EPOCH. And we do know that a substantial number of patients would relapse. And the majority of these would relapse within the first year of having received chemotherapy or not respond to it at all,” Dr. Kamdar explained.

“With the advent of CAR T-cell therapy, they made a huge splash.”

What is Breyanzi?

Breyanzi is made by Bristol Myers Squibb and is approved for the treatment of adults with relapsed or refractory CLL who have not responded to two or more prior lines of therapy.

The drug is the first and only CAR-T cell therapy for CLL to receive accelerated approval from the US Food and Drug Administration (FDA) for previously treated patients with CLL.

The FDA approval was announced last year and was based on the impressive findings from the TRANSCEND CLL 004 trial that studied the effectiveness of Breyanzi in patients with known as relapsed or refractory CLL, a type of disease that has either come back or has not responded well to treatment.

The TRANSCEND CLL 004 study concluded that 91.3% of patients did not have cancer that grew or spread at 12 months of taking Breyanzi, 45% responded to treatment and on average the duration of the response lasted for 35 months, and patients lived about 43 months from the start of the treatment, which is a significant improvement over other treatments.

Additionally, when patients took higher doses of Breyanzi, 18% of them achieved a complete response or remission, including partial bone marrow recovery, meaning the cancer was greatly reduced or, in some cases, completely eliminated.

Breyanzi is recommended for CLL patients who have received at least two previous therapies. It is also approved for patients with or small lymphocytic lymphoma (SLL) under similar circumstances.

“The approval of Breyanzi as the first CAR T cell therapy available for relapsed or refractory CLL or SLL brings new hope to these patients with the potential for durable responses after a single CAR T infusion,” said Dr. Brian Koffman, physician, CLL patient and cofounder, executive vice president and chief medical officer of CLL Society.

“The problem with cancer in general is that the patient’s own T cells — the cells that help fight cancer — unfortunately don’t recognize their own cancer anymore,” Dr. Julie Vose, chair of the Department of Oncology and Hematology at the University of Nebraska Medical Center’s Buffett Cancer Center, tells SurvivorNet.

CAR-T-cell therapy “helps to wake up those cells to be able to fight their own cancer, whereas their own, unmodified cells cannot do that,” she says.

Therapy with Breyanzi works this way:

• Doctors collect a sample of T cells from your blood using a procedure called leukapheresis, then send the sample to a laboratory for processing.
• Lab experts change the T cells in such a way so that they can find and destroy tumor cells.
• After modification, the  lab then multiples the CAR-T cells to create a large population of engineered cells.
• The expanded CAR-T cells are then put back into the patient’s bloodstream, where they can recognize and attack cancer cells.

A patient undergoing CAR-T cell therapy will usually receive about three days of chemotherapy. This chemo helps to get rid of damaged immune systems and gives the new T cells a better chance to fight cancer.

Breyanzi has the potential to reshape the treatment landscape, offering the possibility of one-time infusion therapy instead of continuous treatment, which could reduce the frequency of clinic visits and hospital stays, potentially improving quality of life and treatment outcomes.

How Is Breyanzi Administered?

Breyanzi is a CAR T-cell therapy administered only once via an intravenous (IV) infusion at a certified treatment center. It’s a process that incorporates several steps:

• Blood Collection (Apheresis): The patient’s white blood cells (T cells) are obtained through aphaeresis, a procedure also known as leukapheresis, which takes between 2 to 6 hours.
• Creating Breyanzi: The T cells that are collected from the patient’s body are transported to a specialized laboratory, where they are genetically engineered to become CAR T-cells. This transformation process generally takes about 3 to 4 weeks, though the exact timeline can differ depending on various factors.
• Pre-infusion Chemotherapy: Before a patient receives their Breyanzi infusion, they will undergo a 3-day course of low-dose chemotherapy. This treatment helps suppress other immune cells, reducing the chance that they will interfere with or attack the Breyanzi cells.
• Breyanzi Infusion: Breyanzi is administered through two separate infusions of different cell types, delivered consecutively. Each infusion usually lasts under 15 minutes, but the duration may vary.
• Post-infusion Monitoring: Patient’s will be carefully watched for any side effects while at the treatment center. For the first week, the patient will have daily check-ups, and it’s important to stay near the center for at least 4 weeks to ensure safety.

Potential Side Effects

CAR-T cell therapies are becoming increasingly popular; however, like all medications, they may cause side effects.

The most common side effects associated with the medication include:

• Cytokine release syndrome (CRS), an immune response that can vary from mild, flu-like symptoms to severe, life-threatening conditions
• Neurologic toxicity leading to damage of the nervous system
• Infections
• Laboratory abnormalities including low levels of hemoglobin, neutrophils, and platelet which can lead to fatigue or uncontrolled bleeding
• Secondary cancers. Patients receiving Breyanzi are at risk of developing other cancers.

CRS and neurotoxicity are the primary concerns for patients receiving Breyanzi. These side effects can lead to serious issues such as headaches, fever, rash, rapid heartbeat, breathing difficulties, and low blood pressure.

In more severe cases, inflammation of the central nervous system may occur, resulting in neurological symptoms.

In the TRANSCEND CLL 004 trial, the occurrences of CRS and neurologic events were mostly mild and non-life-threatening, with. 83% of patients experienced CRS and 46% of patients experienced neurologic toxicity.

However, about 1% of those who experienced side effects in the trial died. This is a reminder that despite all the amazing benefits of CAR-T, they are not without risk.

Questions to Ask Your Doctor

Here are some questions you may consider asking your doctor to help understand your treatment options.

• What will my new treatment with Breyanzi cost and how much will my insurance cover?
• How will I feel during treatment?
• Will I have side effects that last after the treatment?
• Should I get a second opinion?
• What are the advantages and disadvantages of Breyanzi
• What is my prognosis?

Contributing: SurvivorNet Staff 

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