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View Clinical TrialsMantle Cell Lymphoma
Mantle cell lymphoma (MCL) is a rare form of B-cell non-Hodgkin lymphoma. B cells are part of the immune system and are made in the bone marrow. If these cells become cancerous, they can turn into a type of cancer called lymphoma. Like all lymphomas, MCL affects the lymphatic system, which includes the lymph nodes, spleen and bone marrow. However, MCL is different because it often also affects the gastrointestinal (GI) tract, including the stomach and colon.
MCL starts when cancerous B-lymphocytes (a type of white blood cell) grow in an area of a lymph node called the mantle zone — a ring of cells that surrounds certain structures inside lymph nodes. In about 10–20% of people with MCL, the cancer doesn’t show up in the lymph nodes at first. Instead, it’s found in the blood and bone marrow. This is called the leukemic phase of MCL.
When the cancerous B cells start to divide too often, they can build up and cause the lymph nodes to swell. For a small number of people, MCL grows slowly. But in most cases, it is aggressive and needs immediate medical attention. As the disease spreads to more lymph nodes and the bone marrow, it reaches more advanced stages.
Mantle cell lymphoma symptoms
MCL is more likely to affect men and people over age 65. Symptoms depend on the areas of the body where the lymphoma develops and usually aren’t detected until the cancer is advanced. Symptoms may include:
- Swollen lymph nodes, especially in the neck, armpits, or groin — this is often the most noticeable symptom.
- Abdominal swelling or discomfort, which may be caused by an enlarged spleen.
- Extreme tiredness, night sweats and unexplained weight loss that gradually gets worse.
- Frequent fevers without an obvious cause.
- High white blood cell count when MCL spreads to the bone marrow.
- Low red blood cells, platelets and neutrophils, which are important for fighting infection.
- Headaches, dizziness or confusion — these may happen if the cancer spreads to the brain or spinal cord.
What does mantle cell lymphoma feel like?
Mantle cell lymphoma usually starts with painless swelling in the neck, armpit or groin. People with MCL might also feel very tired, lose weight without trying, have fevers or sweat heavily at night. Because it can affect the stomach and intestines, it may cause belly pain, bloating or make you feel full quickly. If it spreads to the bone marrow, it can lead to problems like low energy, frequent infections or easy bruising. These symptoms can be hard to notice at first and may seem like other common illnesses, so it’s important to see a doctor if they don’t go away.
Mantle cell lymphoma diagnosis
Generally, MCL patients may note swollen lymph nodes, feel bloating in the abdomen or have a high white blood cell count found during routine blood tests. Sometimes, MCL is found during a routine colonoscopy when colon tissue shows signs of cancer. To confirm MCL, doctors will perform a biopsy of a lymph node, bone marrow or gastrointestinal tissue, followed by special lab tests. The tests look for changes in a gene called TP53 and check for abnormal chromosomes in your cells. If many abnormalities are found, it could mean the MCL is more aggressive or may not respond as well to certain treatments.
This process is called risk stratification. It helps your care team decide which treatments are most likely to work for you and allows them to plan more personalized care. The goal is to give you the best possible outcome based on your unique test results.
Mantle cell lymphoma treatment
MCL is not considered curable, but recent advances in treatment have helped many patients live longer and better lives. People with low- or intermediate-risk MCL often do well for five to eight years or more before the disease returns. In rare cases, especially when the disease is slow-growing (indolent), low-risk and not causing symptoms, patients may not need treatment right away and can be closely monitored instead.
Each person's treatment plan is personalized and based on several factors, including the stage of the lymphoma (early or advanced), symptoms, overall health and any other medical conditions the patient may have. Treatment options include the following:
Radiation therapy
Radiation therapy uses powerful, focused beams of energy to kill cancer cells. There are several different radiation therapy techniques. Doctors can use these to accurately target a tumor while minimizing damage to healthy tissue. Radiation therapy may be offered for limited or localized stage MCL, without high-risk features.
Learn more about radiation therapy.
Targeted therapy
Targeted therapies are designed to interfere with, or target, cancerous cells or the cancer-causing genes that create them.
They are often taken as oral pills and work by blocking a specific enzyme in mantel cell lymphoma cells. This helps stop them from growing and spreading. Sometimes, these oral medications are used along with monoclonal antibodies, a type of immunotherapy, which are given through an IV. Patients taking oral treatments usually don’t need a port (a small medical device placed under the skin, usually in the chest) for IV medicines.
Some common side effects from these drugs may include, fatigue, headache, rash, easy bruising, palpitations, low neutrophil count and infections.
Learn more about targeted therapy.
Stem cell transplantation
A stem cell transplant (also known as a bone marrow transplant) is a procedure that replaces cancerous bone marrow with new, healthy bone marrow stem cells. Depending on the cancer, the healthy stem cells can come from a donor (an allogeneic transplant) or from the patient (autologous). Stem cell transplants are usually given after an intense round of chemotherapy that kills the patient’s existing bone marrow cells. Patients usually must stay in the hospital for three to four weeks after the transplant. This procedure is intense and generally reserved for younger, physically fit patients.
Recent research shows that autologous stem cell transplants are used less often to treat mantle cell lymphoma when BTK inhibitors are given with chemotherapy at the beginning of treatment. These drugs are then continued as maintenance therapy along with a monoclonal antibody, which helps keep the cancer from coming back. At MD Anderson, we do not recommend stem cell transplants for most patients with MCL.
Learn more about stem cell transplants and their side effects.
Chemotherapy
Chemotherapy drugs kill cancer cells, control their growth or relieve disease-related symptoms. Chemotherapy may involve a single drug or a combination of two or more drugs, depending on the type of cancer and how fast it is growing.
A combination of chemotherapy and monoclonal antibody therapy may be used to treat previously untreated MCL. However, because chemotherapy can have serious short- and long-term side effects, weaken the immune system, and newer targeted therapies are showing strong results, most MCL patients now prefer chemotherapy-free treatments.
Chemotherapy may still be used if the symptoms are severe and need to be treated quickly to shrink the tumor(s). In some cases, targeted therapies are also being combined with chemotherapy for older or frail MCL patients.
Learn more about chemotherapy and its side effects.
Monoclonal antibodies
Monoclonal antibodies are a type of immunotherapy. This treatment targets specific markers on the surface of MCL cells. These treatments are often used with targeted therapy and chemotherapy. They have shown significant benefits in helping MCL patients stay in long-term remission.
A combination of immunotherapy and chemotherapy, called chemoimmunotherapy, may also be used, followed by maintenance therapy. This approach has helped improve the overall survival of patients with MCL.
Learn more about immunotherapy and its side effects.
CAR T cell therapy
CAR T cell therapy is a type of immunotherapy. T cells are immune system cells that help the body fight disease by attacking harmful or infected cells. In Chimeric Antigen Receptor (CAR) T cell therapy, a patient’s T cells are collected and genetically modified in a lab to target a specific protein on cancer cells. These modified cells are returned to the patient’s body, where they seek out and attack the cancer cells.
CAR T cell therapy is typically used for people with relapsed or refractory mantle cell lymphoma (meaning their cancer has returned or hasn’t responded to other treatments). It’s not used as a first-line treatment, but rather after other therapies have not worked. However, CAR T cell therapy isn't suitable for every patient with relapsed or refractory MCL because of the possible side effects. Before choosing this treatment, care teams will look at factors like the patient's overall health, other medical conditions and organ function, especially if other treatments have not worked.
Learn more about CAR T cell therapy and its side effects
Leukapheresis
This procedure is used to remove white blood cells (leukocytes) from the blood. It’s often performed on people with very high white blood cell counts, which can occur in certain types of leukemia. It is also used to collect specific white blood cells for treatments or research, such as CAR T cell therapy or stem cell transplants. During the procedure, an intravenous (IV) catheter is placed, and blood is drawn so the excess white cells can be separated and removed. A high white blood cell count can cause serious problems, including bleeding, headaches and tumor lysis syndrome. Tumor lysis can happen when cancer treatment causes cancer cells to break apart quickly, releasing chemicals and toxins into your bloodstream faster than your body can get rid of them.
Leukapheresis doesn’t cure mantle cell lymphoma because it only removes cancerous white blood cells from the bloodstream, not from where the cancer starts, like the bone marrow or lymph nodes. It provides temporary relief from high white cell counts but doesn’t stop the cancer from growing. Long-term treatment requires chemotherapy, targeted therapy, immunotherapy or other cancer-specific treatments.
Lymphoma and Myeloma Center
MD Anderson’s Lymphoma and Myeloma Center is known for its groundbreaking treatments and leading diagnostic techniques.
How BTK inhibitors treat mantle cell lymphoma
B cells are an important part of the immune system. One of their jobs is to neutralize the threat from a foreign invader known as a pathogen. They do this by producing an antibody that binds with the antigen on the threatening entity.
When an antigen binds to a receptor on a B cell, the B-cell receptor signaling pathway is activated. Bruton’s tyrosine kinase (BTK) is an enzyme that’s critical to the activation of the B-cell receptor signaling pathway.
“Without BTK, a B cell can’t function properly,” says lymphoma specialist Michael Wang, M.D.
BTK inhibitors are a type of drug that work to treat cancers caused by defective B cells, such as chronic lymphocytic leukemia, B-cell lymphomas, and Waldenström macroglobulinemia.
Wang has led the pivotal clinical trials that have resulted in the approval of three BTK inhibitors for mantle cell lymphoma by the Food and Drug Administration (FDA). Those BTK inhibitors are ibrutinib, acalabrutinib and, most recently, pirtobrutinib.
“BTK inhibitors have revolutionized therapy options for patients with B-cell lymphomas,” Wang says.
BTK inhibitors stop B cell growth to treat lymphoma
BTK inhibitors work by interfering with the B-cell receptor signaling pathway. When the B-cell receptor signaling pathway goes haywire, B cells can reproduce at an uncontrolled rate and lead to lymphoma. By disrupting the pathway, the abnormal B cells won’t divide. Instead, they will die.
Currently, ibrutinib, acalabrutinib, zanubrutinib and pirtobrutinib are approved to treat patients with mantle cell lymphoma that has relapsed and/or not responded to other treatment.
BTK inhibitors have quality-of-life benefits
BTK inhibitors are administered as an oral pill that are taken daily. “It’s much more convenient for patients,” Wang says.
In addition, patients tend to tolerate BTK inhibitors better than chemotherapy. As published by Wang in the New England Journal of Medicine, almost 70% of patients saw their mantle cell lymphoma tumors shrink by more than 50%.
Possible BTK inhibitor side effects include fatigue, rash, diarrhea, bleeding and bruising. Some patients experience neutropenia, which is caused when a patient’s white blood cell count drops. That means they’re at a higher risk of infection. Patients taking ibrutinib can experience an irregular heartbeat and hypertension. They’re more serious, but both are treatable, Wang says.
“BTK inhibitors are relatively safe drugs, and fortunately, most patients don’t have severe side effects,” Wang says.
And because of the limited side effects, BTK inhibitors are a good option for older patients.
Reversible BTK inhibitors offer patients another option
Ibrutinib was the first BTK inhibitor, but since its approval in 2013, progress has been made to advance the field. Acalabrutinib and zanubrutinib have also become commercially available. All three drugs work in the same way to inhibit the BTK enzyme by irreversibly binding to it. “Once they’re linked, they don’t let go,” Wang says. Because they share the same binding mechanism, if one drug doesn’t work for a patient, neither will the others.
That’s changed with the newer generation of BTK inhibitors. Pirtobrutinib is the first FDA-approved BTK inhibitor that can reverse the binding to the BTK enzyme. “This opens the door to another option, even if a patient has received another BTK inhibitor,” Wang says.
Combination therapies may offer better results with BTK inhibitors
BTK inhibitors have shown to be effective, but researchers are now exploring their use in combination with other therapies.
“The question is: Can we make these drugs work even better and for more patients by pairing them with other drugs?” Wang asks. Studies already show combining ibrutinib and the monoclonal antibody rituximab can benefit patients with newly diagnosed mantle cell lymphoma, as well as some patients whose disease has returned or not responded to treatment.
Lastly, patients may also benefit from BKT inhibitors combined with novel cellular therapies such as CAR T cells and bispecific antibodies. Studies are underway to learn more.
“There’s more to be explored, but BTK inhibitors have already drastically changed treatment for our patients,” Wang says. “With these drugs, patients are experiencing better results with fewer side effects.”
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