FDA approves CAR T cell treatment for resistant mantle cell lymphoma

Mantle cell lymphoma (MCL) is a rare and sometimes ruthless form of non-Hodgkin lymphoma. Even when treatment appears to be successful, the cancer often returns and is difficult to cure.

A new therapy has been approved by the U.S. Food and Drug Administration (FDA) for these most challenging cases: lisocabtagene maraleucel, or Breyanzi. The approval was based on results from a clinical trial led by MSK hematologist oncologist Lia Palomba, MD.

“We now have a good option for a type of lymphoma that has been very difficult to treat when other therapies fail,” Dr. Palomba says. “This is urgently needed because the disease grows more resistant every time it comes back.”

Lisocabtagene maraleucel is a chimeric antigen receptor (CAR) T cell therapy. This form of immunotherapy involves removing T cells from a patient and outfitting them in the lab with receptors that recognize specific targets—known as antigens—on the surface of a cancer cell.

This type of CAR T treatment targets an antigen called CD19, a strategy that was first proposed in 2003 by MSK physician-scientist Michel Sadelain, MD, Ph.D., a pioneer in CAR T cell research.

Clinical trial results for lisocabtagene maraleucel

The trial tested lisocabtagene maraleucel in 88 patients with relapsed or resistant MCL who had already received at least two kinds of therapy, including a targeted therapy called a Bruton’s tyrosine kinase (BTK) inhibitor.

• 83% of patients responded to the treatment, meaning it reduced the cancer;
• 72% of patients had a complete response to the treatment, meaning the cancer disappeared completely;
• The median progression-free survival (time until the cancer began growing again) was 15.3 months.
• Side effects were tolerable and reversible in most cases.

The trial had no control group, meaning it did not compare lisocabtagene maraleucel to another standard treatment. But Dr. Palomba says the CAR T cell treatment worked well in patients who had already received many lines of therapy—up to 11 in some cases. In those patients, standard therapy didn’t work for long.

“Approval of this treatment will offer some hope for patients who in most cases would have reached the end of the line,” she says.

Giving lisocabtagene maraleucel sooner

Dr. Palomba says the positive results support giving lisocabtagene maraleucel earlier to patients with high-risk features of the disease—rather than waiting until other treatments fail. This CAR T cell treatment could possibly be part of a second-line or even first-line therapy for selected patients.

Lisocabtagene maraleucel has already been approved by the FDA for three other distinct subtypes of non-Hodgkin lymphoma. Dr. Palomba’s research played a major role in the treatments approved for two of these types—diffuse large B cell lymphoma and follicular lymphoma.

The approval for mantle cell lymphoma marks another landmark achievement for CAR T cell therapies originating at MSK, where lessons in the lab and the clinic are shared efficiently, creating a unique ecosystem of discovery.

“This treatment was born out of investigations in MSK labs that we have been able to adjust and modify in the clinic,” Dr. Palomba says. “I have led trials, along with MSK hematologic oncologist Jae Park, MD, testing different iterations of the CAR T cells so they will be more persistent and effective. Fundamentally, these therapies have completely changed the outcome of people with aggressive lymphomas.”