Mantle Cell Lymphoma

August 15, 2024

This page was reviewed under our medical and editorial policy by Alex Herrera, M.D., associate professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope^® Cancer Center Duarte

Mantle cell lymphoma, a type of non-Hodgkin lymphoma, is a rare and often aggressive cancer that affects white blood cells called B cell lymphocytes. About 5% of non-Hodgkin lymphomas are mantle cell lymphomas. It is also called mantle zone lymphoma or simply MCL.

What Is Mantle Cell Lymphoma?

Mantle cell lymphoma is one of more than 60 subtypes of non-Hodgkin lymphoma. It takes its name from where it begins — in the mantle zone of lymph nodes. This is a ring of cells surrounding small structures within lymph nodes called germinal centers. Mantle cell lymphoma affects a type of white blood cell called B cells. A very rare subtype of non-Hodgkin lymphoma, it is most common in adults over 60 years of age and is far more common in men than women.

In mantle cell lymphoma, genes within white blood cells called B cell lymphocytes mutate, or change, and begin to grow abnormally, dividing earlier and more often than they should. Mantle cell lymphoma tends to begin as an indolent, or slow-growing, lymphoma. Over time, it may become aggressive as its rate of growth increases.

Mantle cell lymphoma tends to be diagnosed in advanced stages, when the cancer has spread to lymph nodes and bone marrow. It also might be found in the spleen, esophagus, stomach, intestines or bloodstream.

Mantle Cell Lymphoma Symptoms

Most people have symptoms when they are diagnosed with mantle cell lymphoma.

It is common to have:

• At least one swollen lymph node — typically in the neck, underarm or groin — that tends to be painless
• Weight loss
• Fatigue
• Loss of appetite

Other symptoms of mantle cell lymphoma may include:

• Fever
• Night sweats
• Gastrointestinal issues, including nausea, vomiting, indigestion, stomach pain or bloating

What Causes Mantle Cell Lymphoma?

Mantle cell lymphoma is caused by genetic changes in B cell lymphocytes within the mantle zone of lymph nodes.

In most cases, this genetic change begins when small pieces of chromosome 11 and chromosome 14 swap places. This change on chromosome 11 happens at the site of the gene that makes a protein called cyclin D1. As a result, B cells make too much cyclin D1, fueling the growth of more cancer cells.

Sometimes, though less commonly, other genetic changes cause B cells to make too much cyclin D1. Very rarely, genetic changes may cause too much of other cyclin proteins, such as cyclin D2 or cyclin D3.

Even though the majority of mantle cell lymphomas are caused by the same genetic change, they may still vary greatly in how they grow, behave and respond to treatment.

Mantle Cell Lymphoma Risk Factors

There are few known risk factors that might make someone more likely to develop mantle cell lymphoma, though age and sex may play a role. People diagnosed with mantle cell lymphoma tend to be over 60 years of age. Men are also three times more likely than women to develop mantle cell lymphoma.

Mantle Cell Lymphoma Diagnosis

Diagnosing mantle cell lymphoma may involve several types of tests. The only way to know for sure whether mantle cell lymphoma is present is through a biopsy, where a surgeon removes a small piece of tissue from the lymph node and a pathologist examines it under a microscope. For mantle cell lymphoma, this typically is done through an excisional biopsy, in which the affected lymph node is removed, along with some healthy tissue around it.

With the tissue from the biopsy, the pathologist will look for characteristics of mantle cell lymphoma, such as:

• Certain proteins (markers) on the surface of B cells
• High levels of cyclin D1 protein within the cells
• Segments of chromosomes 11 and 14 that have swapped places

The pathologist may also be able to tell if the mantle cell lymphoma is a common form or a rarer variant, which will help inform the treatment plan.

Imaging tests like computed tomography (CT) scans or positron emission tomography (PET) scans might be done during the diagnostic process in order to rule out other factors causing symptoms, or after diagnosis to help find the precise locations of the cancer or to monitor how it is responding to treatment.

Mantle Cell Lymphoma Stages

Staging is the process of understanding the extent of disease or how much cancer has spread. It is an important part of crafting a treatment plan that is most appropriate for each patient and type of cancer.

Imaging tests to determine the stage of cancer include CT scan, PET scan, chest X-ray, magnetic resonance imaging (MRI) scan and ultrasound. These tests may help doctors understand where cancer is, and the tests will vary based on the area of the body, or type of organ, that needs to be explored in more detail.

The stages of mantle cell lymphoma are the same as those for other lymphomas, including both Hodgkin lymphomas and non-Hodgkin lymphomas. Lymphomas have four stages and use a system called the Lugano classification to define the stage of disease.

Stage 1 cancer cells are either:

• Confined to a single lymph node or a group of lymph nodes close to one another (stage 1).
• Found in one organ outside the lymph nodes and lymph system (stage 1E).

Stage 2 cancer cells are either:

• In two lymph node regions, both either above or below the diaphragm, a muscle between the chest and abdomen that is used as a reference point in lymphoma staging.
• In one lymph node region and one nearby organ not in the lymph system, both either above or below the diaphragm (stage 2E).

Stage 3 cancer cells are found in at least one lymph node region above the diaphragm and one below it, potentially involving either a lymph node area or the spleen.

Stage 4 cancer is found in at least one organ outside the lymph system, such as the liver, lung or bone marrow.

For any of these stages, the letters “A” or “B” might be added to be more descriptive. A certain set of symptoms — unexplained fever, night sweats or unexpected weight loss of 10% of body weight or more within six months — are called “B” symptoms. Therefore, adding the letter “B” to the stage describes a cancer that also causes “B” symptoms, such as stage 2B. Cancers that do not cause these symptoms may have “A” added to the stage, such as stage 1A.

Mantle Cell Lymphoma Treatment

Most mantle cell lymphomas are aggressive, meaning they grow quickly. But for slower-growing types that aren't causing symptoms, treatment may not begin immediately after diagnosis. Instead, doctors may recommend a strategy called “watchful waiting,” in which they monitor the cancer’s progression over time.

Imaging tests will be done regularly, and treatment may begin as soon as symptoms start to show.

For all other mantle cell lymphomas, treatment begins soon after diagnosis and is highly dependent on the patient’s overall health, age and the type of mantle cell lymphoma they have. There’s no one standard regimen of treatment for mantle cell lymphoma, but a common treatment is a monoclonal antibody called rituximab used in combination with other drugs.

Some common combinations are listed below.

BR: bendamustine and rituximab

R-CHOP: rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone

VR-CAP: bortezomib, rituximab, cyclophosphamide, doxorubicin and prednisone

R2: lenalidomide and rituximab

R-DHAP: rituximab, dexamethasone, cytarabine and cisplatin

Rituximab may also be used after treatment as a maintenance therapy to keep cancer from recurring.

For younger patients, high-dose chemotherapy may sometimes be paired with a stem cell transplant, also called a bone marrow transplant. In this treatment, chemotherapy is given at a very high dose in order to destroy cancer cells, but it also damages bone marrow. After chemotherapy, healthy bone marrow cells are infused back into the body, either from a donor or cells collected from the patient before chemotherapy began.

Recurrent or Hard-to-Treat Mantle Cell Lymphoma

Some mantle cell lymphomas fail to respond to treatment or return after treatment is over. Of mantle cell lymphomas that come back, most recur within two years of the end of treatment.

One type of treatment for recurrent mantle cell lymphoma is an immunotherapy called chimeric antigen receptor (CAR) T cell therapy. It involves taking a type of white blood cell called T cells from a patient’s blood and engineering them in a laboratory to include special receptors that attack cancer cells.

These CAR T cells are infused back into the bloodstream where they multiply quickly and begin finding and attacking cancer. CAR T cell therapy is a treatment option for mantle cell lymphoma that has recurred after treatment, as well as mantle cell lymphoma that has not responded to other treatment types.

Other types of therapies that are used for recurrent or hard-to-treat mantle cell lymphomas include bortezomib, lenalidomide and the Bruton tyrosine kinase (BTK) inhibitors ibrutinib, acalabrutinib and zanubrutinib.

Many clinical trials are underway to explore new treatment options, including new combinations of existing drugs and comparing existing therapies to one another.

Mantle Cell Lymphoma Survival Rate

According to the National Cancer Institute, the five-year relative survival rate for mantle cell lymphoma is 55.6%, meaning that more than half of people were alive five years after their diagnosis in the most recent data collected. For people between 20 and 64 years of age, this rate is 67.5%. For those 65 years and older, it is 46%.

It is important to remember that survival rates are based on data from people who had the cancer years ago, and they do not predict what will happen to any individual patient. These rates do, however, give patients and their families an idea about their prognosis.

As research continues and treatments improve, the five-year relative survival rate for mantle cell lymphoma has improved over time, especially for adults between 50 and 64 years of age and those diagnosed with Stage 4 mantle cell lymphoma.