MD Anderson at ASH

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, or MALT lymphoma, is a slow-growing type of non-Hodgkin lymphoma that develops in the lymphoid tissue outside the lymph nodes.

MALT lymphoma is the most common form of marginal zone lymphoma, though it’s still rare. It’s estimated that about 5,000 new cases of MALT lymphoma are diagnosed in the U.S. each year, according to lymphoma specialist Dai Chihara, M.D., Ph.D.

To learn more about this disease, we spoke with Chihara and radiation oncologist Jillian Gunther, M.D., Ph.D. Here’s what they shared.

Where does MALT lymphoma develop?

The stomach is the most common site for MALT lymphoma. This is known as gastric MALT lymphoma. It can also be found in other parts of the gastrointestinal tract.

“It’s important to note that this is not a primary stomach cancer,” says Gunther. “This is lymphoma that occurs in the stomach.”

Non-gastric MALT lymphoma most commonly affects the lungs, salivary glands, tissues around the eye and skin.

What are the symptoms of MALT lymphoma?

Symptoms can vary, depending on where the lymphoma is in the body. Some people may not have any symptoms, and the cancer is found incidentally when a doctor is testing for something else.

For gastric MALT lymphoma, symptoms often mimic those of an upset stomach and can include:

• abdominal pain
• bloating
• heartburn
• acid reflux

Non-gastric MALT lymphoma may cause the following symptoms, depending on where it occurs in the body:

• salivary gland: a mass you can feel or that shows up in imaging
• lung: cough or shortness of breath
• skin: a small bump on the skin that can resemble a bug bite or pimple

“If you have any of these symptoms for longer than a couple of weeks without improvement, or if the symptoms are worsening, you should see a doctor to be evaluated,” says Gunther.

What causes MALT lymphoma?

Some MALT lymphomas are associated with autoimmune disorders and infections, depending on where the lymphoma is located.

Helicobacter pylori (H. Pylori) infection, a common bacterial infection that can cause stomach ulcers, increases the risk for gastric MALT lymphoma. Many gastric MALT lymphoma patients will have an H. Pylori infection.

“The H. Pylori infection causes chronic inflammation in the stomach, which is thought to increase the risk of gastric MALT lymphoma,” says Chihara. 

MALT lymphoma on the skin may be linked to Borrelia burgdorferi infection, while the autoimmune disorder Sjogren’s syndrome can increase the risk of MALT lymphoma in the salivary glands.

How is MALT lymphoma diagnosed?

Doctors need biopsies to diagnose MALT lymphoma. The type of biopsy depends on where the lymphoma has developed.

An interventional radiology image-guided biopsy may be used to diagnose MALT lymphoma in the salivary glands or lungs. A bronchoscopy can also be used for the lungs.

An endoscopy may be used to diagnose gastric MALT lymphoma.

After a MALT lymphoma diagnosis is made, doctors will try to determine the cancer stage.

“With MALT lymphoma, it’s more common for patients to be diagnosed with early-stage disease, or localized disease that hasn’t spread to distant lymph nodes or other parts of the body,” says Gunther.

The cancer’s stage determines the treatment. 

How is MALT lymphoma treated?

Patients with gastric MALT lymphoma can be given antibiotics first to treat H. Pylori. Treating the infection often clears away the lymphoma.

If antibiotics don’t work, patients with early-stage MALT lymphoma receive radiation therapy.

If MALT lymphoma is not localized, and if you’re not experiencing any problems from the cancer, your doctor may choose to monitor you closely, rather than prescribing treatment.

“MALT lymphoma is often a very slow-growing disease, and people can live with it for long periods, sometimes without even knowing they have it,” says Gunther. “MALT lymphoma is treatable in most cases. We don’t want to cause the patient more harm with the treatment than the disease itself.”

For patients with progressive advanced-stage MALT lymphoma that is causing symptoms or trouble, there are systemic treatment options.

The first systemic treatment option is the monoclonal antibody rituximab or chemoimmunotherapy, which is a combination of chemotherapy and immunotherapy. You may be given a chemotherapy drug, such as CHOP or bendamustine plus rituximab.

Recurrent MALT lymphoma may be treated with oral drugs, such as BTK inhibitors ibrutinib and zanubrutinib, or the immunotherapy drug lenalidomide.

What new research is being done to advance MALT lymphoma treatment? 

Gunther recently led a clinical trial looking at reducing the radiation dosage for gastric MALT lymphoma patients.

“In the past, the standard dose for radiation was at least two-and-a-half weeks of treatment. But because of the positive response to low-dose radiation in this type of cancer, we’ve been looking to reduce the dose,” explains Gunther.

In the clinical trial, patients started with ultra-low-dose radiation, or just two days of treatment.

“We gave additional treatment — another 10 days of radiation — only to those patients who did not experience a complete response after the initial two days,” she says. “This spared a majority of patients unnecessary treatment and side effects.”

Because MALT lymphoma is rare, more research is needed to help determine which treatments work best for patients with MALT lymphoma. But Chihara notes that MD Anderson continues to pursue new clinical trials with the goal of expanding treatment options for patients with MALT lymphoma.

Request an appointment at MD Anderson online or by calling 1-877-632-6789.

For many patients diagnosed with certain types of B-cell lymphoma, leukemia and multiple myeloma, chimeric antigen receptor (CAR) T cell therapy offers an effective treatment option. This cellular therapy is created by extracting a patient’s T cells, modifying them in a lab to identify and attack cancer cells, and returning them to the patient.

The process of creating the CAR T cells can take three to four weeks. Radiation therapy can be a tool to help get a patient through this manufacturing period. This is called bridging therapy.

“Bridging therapy can help control the disease so that a patient can get to the CAR T cell infusion,” says radiation oncologist Penny Fang, M.D. Research from Fang and her colleagues examines the role of bridging therapy for B-cell lymphoma patients receiving CAR T cell therapy. Their latest findings will be presented at the 2023 American Society for Radiation Oncology Annual Meeting.

Radiation therapy can relieve cancer-related symptoms

Currently, bridging therapy is often used ahead of CAR T cell therapy in patients who have large tumors or tumors that are causing symptoms such as pain or weakness. It can also be used to reduce the risk of symptoms in patients with tumors in or near important areas of the body.

Patients who have had prior radiation may still be eligible for bridging therapy, Fang says.

Ongoing work examines the effect of radiation therapy on CAR T cell therapy efficacy

In addition to managing tumor-related symptoms, radiation therapy reduces the number of tumor cells. “By scaling down the job for the CAR T cells, we can potentially optimize their success,” Fang says.

The more tumor cells that are eliminated with radiation therapy before CAR T cell therapy, the less work the CAR T cells have to do. “Ultimately, the goal of CAR T cell therapy is cure, and we hope to help get there with radiation therapy,” Fang says.

At the ASTRO Annual Meeting, Fang and her colleagues will present findings that show patients who can feasibly be treated with radiation therapy at all the involved tumor sites tend to have more favorable outcomes.

 “We have ongoing work now to try to understand why that may be the case,” Fang says.

Bridging therapy may prime the tumor microenvironment and the tumor cells

Reducing the tumor volume may not be the only benefit of bridging therapy. Fang and her colleagues are conducting clinical trials to explore the advantages of radiation therapy in patients receiving CAR T cell therapy. They’re looking at whether lower dose radiation can help modify the tumor microenvironment and help with tumor cell death. 

“We’re studying whether therapy may be priming the tumor microenvironment and/or systemic immune state so that the CAR T cells may more effectively do their work,” Fang says.

Radiation therapy may benefit patients who don’t experience a complete response to CAR T cell therapy

Fang and her colleagues also are investigating whether radiation therapy can be used to modify the immune response and jumpstart idle CAR T cells in patients who don’t experience a complete response to CAR T cell therapy.

An ongoing study is investigating whether radiation may be synergistic with CAR T cell therapy in patients with multiple myeloma who don’t completely respond to treatment. “Our question is: if there’s disease resistant to CAR T cells, can we potentially improve the response with radiation,” Fang asks.

Research aims to expand understanding of radiation therapy’s impact on CAR T cell therapy

Fang and her colleagues are conducting more research to better understand the synergy of radiation therapy and CAR T cell therapy. For example, they have an ongoing umbrella clinical study looking at patients across multiple hematologic malignancies who are being treated with radiation therapy and CAR T cell therapy.

“We’re also planning to analyze patients’ blood biomarkers so that we can better quantify the immune response after radiation therapy and how it may potentially synergize with CAR T cell therapy to improve outcomes for more patients,” Fang says.

Request an appointment at MD Anderson online or by calling 1-877-632-6789.