What Is Mantle Cell Lymphoma, and How Is It Treated at RCCA?

Key Takeaways

• Mantle cell lymphoma (MCL) is a rare and aggressive type of lymphoma, a form of blood cancer, that starts in the mantle zone of lymph nodes and spreads quickly to other organs.
• Most cases of MCL do not cause symptoms at first. When symptoms develop, they usually include swollen lymph nodes, abdominal bloating, fatigue, fever, night sweats, weight loss, and gastrointestinal (GI) complaints.
• MCL is diagnosed with a lymph node biopsy and an immunohistochemistry test to identify hallmark proteins.
• Treatments for MCL include chemotherapy, immunotherapy, targeted therapy, and stem cell transplantation.

What Is Mantle Cell Lymphoma?

Lymph nodes are small, bean-shaped structures that help the body fight infection, disease and potentially harmful foreign substances. The body contains several hundred lymph nodes, with high numbers of these structures located in the armpits, the sides of the neck, the chest, and groin.

Each lymph node has a so-called mantle zone, an outer ring of B-lymphocytes (white blood cells) that surrounds the center of the node. Mantle cell lymphoma (MCL) is a type of lymphoma that starts in the mantle zone. MCL occurs when some of the B-lymphocytes develop a genetic mutation that causes them to reproduce uncontrollably. These mutated cells are the cancer.

The CCND1-IGH translocation, also known as t(11;14), is the hallmark of mantle cell lymphoma. It is a specific genetic change in which chromosomes 11 and 14 break and trade sections. Over 95% of mantle cell lymphoma cases contain this mutation.

How Common Is Mantle Cell Lymphoma?

Mantle cell lymphoma is a comparatively rare type of blood cancer. It accounts for around 6% of all non-Hodgkin lymphoma diagnoses, with about 0.5 to 1 new case per 100,000 people diagnosed annually. It occurs most often in men over the age of 60, although anyone can get mantle cell lymphoma at any age.

What Are Symptoms of Mantle Cell Lymphoma?

Most cases of mantle cell lymphoma do not cause symptoms early on. As a result, the disease often goes unnoticed until it develops further. This fact, combined with the cancer’s tendency to spread quickly to other organs, means that MCL is often diagnosed when it is already in late stages. About 70% of MCL diagnoses are in Stage IV. When symptoms develop, they may include:

• Swollen lymph nodes: Primary lymphoma tumors form in the lymph nodes, causing painless swelling in the neck, armpits, and/or groin.
• Abdominal bloating: Mantle cell lymphoma that spreads to the abdominal lymph nodes or the spleen may cause pain or a full feeling.
• Fatigue: Aggressive cancers steal energy from the patient’s metabolism to grow, causing persistent fatigue and weakness.
• Gastrointestinal symptoms: Mantle cell lymphoma that spreads to the gastrointestinal system may cause diarrhea, constipation, or bloody stool.
• B symptoms: Like other lymphomas, MCL causes classic “B symptoms,” including unexplained fevers above 100.4 degrees Fahrenheit, drenching night sweats, and weight loss.

Because MCL rarely causes symptoms in its early stages, most cases are detected when physicians explore the cause of abnormal results on a routine blood test.

How Is Mantle Cell Lymphoma Diagnosed?

Primary care physicians and other providers typically refer a patient to a hematologist when blood test results indicate the possible presence of lymphoma. The hematologist’s evaluation includes a thorough history and physical examination, as well as specialized tests, such as:   

Lymph Node Biopsy

A lymph node biopsy is the definitive test for diagnosing mantle cell lymphoma. The physician will use a hollow needle to take a sample of tissue and fluid from a lymph node. Alternatively, the whole lymph node may be surgically removed for testing. The sample is sent to a medical laboratory where it is studied under a microscope for cancer cells.

The tissue sample is also used for an immunohistochemistry (IHC) test. This test uses lab-made antibodies attached to dyes to stain specific proteins, making them easy to see under a microscope. For MCL, pathologists look for cyclin D1. The t(11;14) mutation, which is the hallmark of MCL, causes an overproduction of the cyclin D1 protein. If high quantities of cyclin D1 are found, the pathologist can confirm the presence of mantle cell lymphoma.

Biomarker Testing

After diagnosing MCL with a biopsy and IHC test, pathologists will proceed to biomarker testing. This phase further confirms the diagnosis while providing more information about the patient’s cancer. Types of biomarker testing used for lymphoma include:

• Flow cytometry: Cells in a fluid stream are passed in front of a laser. Light scatter and color tags are used to measure each cell and locate specific markers.
• FISH: Fluorescence in situ hybridization uses fluorescent probes to detect specific DNA sequences and abnormalities, including the t(11;14) translocation.

Ki-67 Proliferation Index

Next, pathologists often will perform a Ki-67 proliferation index. This test counts the percentage of cells that contain the Ki-67 protein. This protein is present only when cells are actively dividing, making it a useful indicator for how quickly the cancer is spreading. The Ki-67 proliferation index is used to predict the cancer’s behavior and determine patient prognosis, or outlook.

Bone Marrow Biopsy

The next step is to determine how far the mantle cell lymphoma has spread. A bone marrow biopsy is performed to assess whether the lymphoma has spread into the bone marrow. The physician uses a hollow needle to remove a liquid sample and a tiny piece of bone tissue from the hip. These samples are studied under a microscope to look for lymphoma cells.

What Are the Stages of Mantle Cell Lymphoma?

In addition to diagnosing mantle cell lymphoma, the testing process also provides information about staging. Like other lymphomas, mantle cell lymphoma is staged based on the Ann Arbor system. This system divides the body in half horizontally (above and below the diaphragm) to depict the extent to which lymphoma has spread through the body via the lymphatic system. The four stages are defined as follows:

• Stage I: Cancer cells are found in only one lymph node group.
• Stage II: Cancer cells are found in two or more lymph node groups, but all are on the same side of the diaphragm.
• Stage III: Cancer cells are found in lymph node groups on both sides of the diaphragm.
• Stage IV: Cancer cells are found in one or more organs outside the lymphatic system, such as the bones, lungs, liver, or GI tract.

Because MCL spreads aggressively, most new diagnoses are made in Stage IV, when the cancer has already spread outside the lymphatic system.

What Is MIPI Risk Stratification?

The MIPI (Mantle Cell Lymphoma International Prognostic Index) is a tool for predicting survival in patients with mantle cell lymphoma. It takes the following factors into account:

• Age: Younger patients are likely to survive longer than older individuals.
• ECOG performance: The Eastern Cooperative Oncology Group Performance Status score evaluates a person’s overall physical health to determine the patient’s ability to tolerate aggressive treatments.
• Lactate dehydrogenase (LDH): LDH is an enzyme that is released by body tissues when they are damaged. High LDH levels indicate severe tissue damage throughout the body.
• White blood cell count: MCL can significantly elevate WBC counts. Extremely high WBC counts can lead to health crises that threaten survival.

These factors are used to sort patients into low, intermediate, and high-risk categories. Prognosis is predicted based on risk category, with lower-risk patients expected to live longer than high-risk ones.

Indolent vs. Aggressive MCL

Prognosis also depends on whether the MCL is indolent or aggressive. MCL ranges from a slow-growing, indolent form to a fast-growing, aggressive form. The primary subtypes include:

• Leukemic non-nodal MCL: This is an indolent subtype of MCL that primarily affects the blood, bone marrow, and spleen, often sparing the lymph nodes and GI tract.
• Classic MCL: This is the most common form of MCL and is typically aggressive. It starts in the lymph nodes but spreads quickly to the spleen, liver, and GI tract.
• Blastoid MCL: This rare subtype is extremely aggressive. It features lymphoma cells that look immature and reproduce extremely quickly, leading to a rapid growth rate.

Aggressive subtypes require prompt and aggressive treatment. Indolent types, on the other hand, can sometimes simply be monitored.

How Is Mantle Cell Lymphoma Treated?

The best treatment for mantle cell lymphoma depends on the disease’s stage, subtype, and MIPI score. RCCA oncologists develop personalized plans for every patient they treat to ensure the best possible outcome, whether the goal is full remission or long-term management.

For Transplant-Eligible Patients

Bone marrow transplant is the most effective treatment for MCL. For patients who can tolerate it, the following treatment plan is implemented:

Induction

Induction chemotherapy is the first treatment. It is administered to kill as many cancer cells as possible to reduce the cancer’s presence in the body. One of three regimens may be used:

• R-CHOP: This regimen combines targeted therapy, chemotherapy, and a steroid to kill cancer cells. Each letter in R-CHOP stands for a specific medicine used.
• Cytarabine-based induction: This is an intensive type of chemotherapy used for acute blood cancers. The drug works by stopping cancer cells from making new DNA.
• Nordic regimen: For young, fit patients, this is an alternating regimen of R-CHOP and cytarabine-based induction to aggressively eliminate cancer.  

Radiation therapy may also be employed to target the cancer cells during the induction stage.

Consolidation

The consolidation phase begins after the patient has recovered from induction. The goal is to destroy any lingering cancer cells to reduce the likelihood of a relapse. In autologous transplantation, physicians collect a sample of healthy stem cells from the patient, then administer a high dosage of chemotherapy to kill any remaining cancer. The stem cells are retransplanted into the bone marrow to help rebuild the immune system. (In allogeneic transplantation, stem cells from a compatible donor are infused.)

Maintenance

The final phase is maintenance. Rituximab immunotherapy is administered to kill any cancer cells that survived consolidation and prevent the lymphoma from returning.

For Transplant-Ineligible Patients

While stem cell transplantation is highly effective, it is also intensive. Some patients may not be healthy enough to withstand the side effects. For those deemed ineligible for transplantation, the following treatments may be recommended:

• BR: This combination of bendamustine chemotherapy and rituximab immunotherapy is effective and easier for less-healthy patients to tolerate.
• R-CHOP: This combined treatment is often recommended for older patients.
• Ibrutinib: This emerging first-line treatment blocks the proteins that MCL uses to grow. It works well at achieving remission when other treatments fail.

Relapsed MCL

The management of relapsed or returning MCL treatment is evolving rapidly thanks to cutting-edge new treatments. Bruton’s tyrosine kinase (BTK) inhibitors such as ibrutinib are a targeted therapy that blocks the proteins that tell lymphoma cells when to divide. This effectively halts the cancer’s spread and kills cells that can’t reproduce. Venetoclax and pirtobrutinib are other targeted therapies that may work well on cancer that relapses after ibrutinib.

Chineric antigen receptor T-cell (CAR T-Cell) Therapy

CAR T-cell therapy is another cutting-edge treatment. It involves taking a sample of white blood cells from the patient to be modified in a laboratory. The altered cells are multiplied, then infused back into the patient’s body, where they hunt and kill cancer. CAR T-cell therapy is often effective at eliminating MCL when other treatments fail.

Find Mantle Cell Lymphoma Treatment Near You in NJ, CT, MA, and the Washington, D.C., Area

While mantle cell lymphoma is aggressive, many patients enjoy long survival and a high quality of life with the correct treatment. Regional Cancer Care Associates (RCCA) offers specialist care for mantle cell lymphomas well as access to clinical trials. We serve patients at more than 20 locations near you across New Jersey, Connecticut, Massachusetts, and the Washington, D.C., area. Contact RCCA today to learn more or get started.

Frequently Asked Questions About Mantle Cell Lymphoma

What is a mantle cell lymphoma?

Mantle cell lymphoma is a rare type of non-Hodgkin lymphoma. It starts in cells in the “mantle zone,” which is the outer ring of lymphocytes (white blood cells) that surround the center of a lymph node. Although it occurs infrequently, it is one of the most aggressive types of lymphoma.

How is mantle cell lymphoma different from other lymphomas?

Mantle cell lymphoma has a unique growth pattern that makes it difficult to categorize. It has small cells that resemble an indolent (slow-growing) lymphoma under a microscope, but which often behave aggressively. Unlike other lymphomas, which remain confined to the lymphatic system, mantle cell lymphoma frequently spreads into the spleen, blood, and gastrointestinal system.

Is mantle cell lymphoma curable?

Mantle cell lymphoma is not considered curable. The cancer has a high likelihood of returning over time, and treatments rarely cure it completely. However, treatments are often effective at bringing the cancer into long-term remission. Patients can survive for many years with a high quality of life, with their cancer either fully inactive or managed like a chronic condition.

What are the treatment options for mantle cell lymphoma?

Treatment options for mantle cell lymphoma depend on the cancer’s stage, how quickly it is growing, and the patient’s overall health. Slow-growing, early-stage lymphoma can be monitored with active surveillance. Aggressive cases may be treated with immunotherapy, targeted therapy drugs, stem cell transplants.

What is a BTK inhibitor and how does it treat MCL?

A BTK inhibitor is a targeted therapy drug that blocks the BTK protein. The BTK protein tells cells when to grow. Some lymphoma cells produce excess quantities of the protein, causing uncontrolled growth. By blocking this protein, the drug prevents the cancer from growing. The cancer stops spreading and starts to die.

What is CAR T-cell therapy for mantle cell lymphoma?

CAR T-cell therapy is a type of immunotherapy treatment. Doctors take a sample of the patient’s white blood cells and modify them in a laboratory to hunt cancer. The modified cells are multiplied in large numbers, then infused into the patient’s body, where they will find and destroy lymphoma cells.

What is the survival rate for mantle cell lymphoma?

The five-year survival rate for mantle cell lymphoma is about 50%. An individual patient’s survival depends on the person’s age, overall fitness level, and how aggressive their cancer is. Survival rates are improving with new treatments and improvements to older modalities.

What is the MIPI score for MCL?

The MIPI (Mantle Cell Lymphoma International Prognostic Index) is a clinical tool for determining a patient’s likely disease course. It is calculated based on the patient’s age, physical fitness, blood enzymes, and white blood cell count to stratify patients into low, intermediate, and high-risk categories. Higher-risk categories require more aggressive treatments and have a lower median overall survival.