New CAR T-Cell Therapy Approved for MCL

Hope is on the horizon for mantle cell lymphoma patients as a new therapy was approved by the U.S. Food and Drug Administration (FDA) to treat this aggressive cancer. 

This immunotherapy, called lisocabtagene maraleucel or liso-cel (Breyanzi, BMS), uses the patient’s own re-engineered T-cells to attack and destroy the mantle cell lymphoma. 

This is the fourth subtype of non-Hodgkin lymphoma for which this liso-cel CAR-T has received FDA approval, making it the CAR-T therapy available to treat the widest array of B-cell malignancies. 

What Is Mantle Cell Lymphoma? How Do MCL Patients Respond to Treatment? 

Mantle cell lymphoma (MCL) is a rare type of non-Hodgkin lymphoma (NHL) and is currently incurable. Though initial therapies for newly diagnosed patients exist, people with MCL will often relapse or become unresponsive (refractory) to those treatments after a short amount of time. 

As the disease returns, the cancer usually comes back stronger and harder to beat.

However, doctors and researchers are working tirelessly to find new treatment alternatives for patients with MCL.

In the US alone, there are more than 80 open clinical trials (July 2024).

Learn more about MCL and its treatment with HealthTree’s 101 articles: Mantle Cell Lymphoma 101.

What is CAR T-Cell Therapy?

Breyanzi is an immunotherapy, meaning the mechanism of action partners with the patient’s immune system to fight the cancer. 

This specific immunotherapy is a CAR T-cell therapy, in which a patient’s T-cells are harvested, sent to a lab to be re-engineered to identify better and eliminate cancer cells, and readministered to the patient. 

The FDA first approved CAR T-cell therapy occurred in 2017 for acute leukemia. Since then, other CAR-Ts have been evaluated, approved, and widely used to treat other blood cancers, such as large B-cell lymphoma and multiple myeloma. While it has potential risks, such as infection and neurological side effects, it also has the potential for great reward. 

Who Qualifies for Breyanzi? 

Adults diagnosed with mantle cell lymphoma who have received at least two prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor.

Breyanzi Clinical Trial Results

In TRANSCEND NHL 001, the clinical trial that led to Breyanzi’s approval in MCL, 85.3% of the 68 patients responded to the treatment, with 67.6% of patients achieving a complete response (CR). 
 

• The median time to respond to the therapy was one month 
• Those responses lasted a median of 13 months 
• More than half of the 68 patients maintained response at 12 months 
• 38.3% of patients maintained response at 18 months after therapy

This level of response is extremely welcomed in a field where there have been few treatment advancements. 

Breyanzi Side Effects 

Breyanzi has a reliable safety profile. While side effects include cytokine release syndrome and neurologic events, the severity of those side effects was consistently low across several clinical trials. 

Cytokine Release Syndrome 

Because CAR T-cell therapy, such as Breyanzi, works with your immune system, when the patient is given the medication, there is a potential for an “immune system overdrive.” When this occurs, the immune system releases certain chemicals called cytokines, and the level of those cytokines within the body can negatively affect patients to varying degrees. 

CRS symptoms are ranked on grade levels 1-4, with 1 being mild symptoms such as a fever, 2 being moderate that might require oxygen, and 3-4 being severe and life-threatening. 

Within a patient population of 702 MCL patients tested across several clinical trials, Breyanzi induced CRS in 54% of patients, with most of those reactions being grades 1-2. Only 3.2% of this population received Grade 3 or higher CRS symptoms.

Neurologic Events 

Neurologic events (such as intense brain fog or inability to read/write) occurred in 31% of patients. Of the 702 patients, 10% had Grade 3 or higher symptoms. 

88% of those patients resolved their issues within 7 days. 

How Is Breyanzi Given to Patients? 

CAR T-cell therapies consist of a one-time infusion via intravenous administration. Breyanzi's encouraging safety profile allows it to be administered in an outpatient setting. In the TRANSCEND NHL 001 trial, patients received the therapy in both in-patient and out-patient settings. 

Action Steps 

If you or your loved one is an MCL patient, ask your treating physician if Breyanzi is right for you. 

You can also ask your provider if there are similar clinical trials near you (or within your country, if appropriate) that you qualify for to advance MCL treatment research and increase your chance of a positive outcome. 

You can search for potential clinical trials here: HealthTree MCL Clinical Trial Finder 

Consider advocating through rare disease foundations to raise mantle cell lymphoma awareness and increase research funds. 

Conclusion

Liso-cel CAR-T (Breyanzi) offers a safe, durable, and successful treatment option to mantle cell lymphoma patients and their loved ones who have experienced relapses or who have become refractory to previous therapies.

With this approval, we hope other pharmaceutical companies can improve outcomes for MCL patients by making this groundbreaking therapy accessible to everyone. 

Sources: 

• Two-year follow-up of lisocabtagene maraleucel in relapsed or refractory large B-cell lymphoma in TRANSCEND NHL 001
• U.S. Food and Drug Administration Approves Bristol Myers Squibb’s Breyanzi as a New CAR T Cell Therapy for Relapsed or Refractory Mantle Cell Lymphoma