This story was originally published as a news story from Northwestern University Feinberg School of Medicine.

Their work led to a breakthrough: CAR T‑cell therapy.

In a clinical trial, this innovative approach improved outcomes for people with relapsed or refractory MZL, helping patients live longer and stay cancer‑free longer. The findings, published in The Lancet, point to a promising option for patients who previously had limited choices.

What is Marginal Zone Lymphoma

Marginal zone lymphoma, or MZL, is a rare and slow-growing type of non-Hodgkin lymphoma. It develops in B-cells, a type of white blood cell, and can affect lymph nodes, the bone marrow and other organs.

MZL makes up about 8% of non-Hodgkin lymphoma diagnoses. The average age of diagnosis is 60, and it is also slightly more common in women than men. 

Many people with MZL have few symptoms and may not need treatment right away. But for some, the disease becomes more aggressive. Even after treatments such as chemotherapy, immunotherapy or targeted therapy, the cancer can return.

When that happens, effective options are limited — making advances like CAR T‑cell therapy especially meaningful.

The Search for Effective Treatment Options

“Historically, patients with MZL who have had one to two treatments in the past struggle with maintaining a long-term response with subsequent therapies,” says Reem Karmali, MD, a hematologist and medical oncologist at Northwestern Medicine and co-author of the study. “We expect diminishing returns with each treatment. This is a population that has been routinely marginalized and not well studied in the setting of a clinical trial; therefore, innovations and new treatments in this group have been slow to develop.”

Doing the Research

Scientists studied CAR T-cell therapy, a type of immunotherapy, to see if it could help people with MZL whose cancer had returned or did not respond to prior treatment.

About the study:

• The trial tested the CAR T-cell therapy, lisocabtagene maraleucel (liso‑cel), in 67 adults with relapsed or refractory MZL.
• All participants had already received at least two previous treatments.
• Patients were treated at 30 medical centers across the United States, Canada, Europe and Japan.

How the therapy works

• Liso‑cel uses a patient’s own T cells, the body’s primary cells for fighting infected and diseased cells.
• Scientists reengineer those cells to recognize and attack a protein found on lymphoma cells.
• Each patient received one dose of liso‑cel after a short course of chemotherapy to prepare the body for treatment.

What scientists found

• The therapy led to strong and lasting responses.
• Two years after treatment:
• 89% of patients who responded were still cancer‑free.
• 86% had no disease progression.
• 90% were still alive.

Quality of life improvements

• Patients reported feeling better overall.
• Many experienced:
• Fewer symptoms
• Better daily functioning
• Improved quality of life after treatment

“These results far supersede results seen with any other therapeutic evaluated in the relapsed/refractory MZL population,” says Dr. Karmali, also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and associate professor of Medicine at Northwestern University Feinberg School of Medicine. “With these findings, liso-cel received FDA approval for the management of MZL in the 3l+ setting and is now available to patients, which is a huge breakthrough.”

Bringing a Breakthrough Therapy to Patients With MZL

The FDA approval means liso-cel is now an option for people with MZL who have tried at least three lines of treatment. Scientists are now studying whether liso-cel could help people earlier in their treatment journey.

“Even in third line, it still produces better results than what we see with currently available treatments used in second line, underscoring the importance of considering liso-cel earlier,” says Dr. Karmali. “There are also other treatments that are being explored in relapsed or refractory MZL that look very promising, including bispecific antibodies. We hope to have a number of other options for treatment of relapsed or refractory MZL in the near future.”

Learn more about cancer research and clinical trials at Northwestern Medicine.