Treatment
Currently, there is no single universally accepted standard or optimal treatment for mantle
cell lymphoma (MCL). Instead, multiple effective treatment options are available, tailored to the disease stage,
patient’s age, and overall health.
MCL is generally considered an aggressive lymphoma, and most patients require treatment at
diagnosis. However, a subset of patients may have an indolent form that can be monitored without immediate treatment.
First-Line Treatment Approaches
Chemotherapy + Monoclonal Antibody Therapy: This combination has been the most commonly used treatment for MCL and remains a mainstay of therapy.
Bruton’s Tyrosine Kinase (BTK) Inhibitors: Increasingly, BTK inhibitors (a type of targeted therapy) are being integrated into treatment, either alone or in combination with monoclonal antibody therapy and/or chemotherapy.
Response to Standard Chemotherapy: While many patients initially respond to chemotherapy, MCL—like some other non-Hodgkin lymphomas—has a high risk of relapse, meaning the disease can return after initial treatment. Moreintensive or newer therapies may help delay relapse for longer periods.
>
Intensive and Maintenance Therapies
For younger, healthier patients—or older patients in excellent condition—a more intensive chemotherapy regimen or stem cell transplant may be considered after achieving remission. However, stem cell transplants are being used less frequently as newer therapies become available.
Maintenance Therapy: Patients may receive monoclonal antibody maintenance therapy, oral targeted therapy, or a combination to help prolong remission and prevent relapse.
Ongoing Research and Clinical Trials
Several clinical trials are investigating the most effective treatment strategies for MCL. If a clinical trial is available, a doctor may recommend it as part of the initial therapy plan.
Treatment Options May Include:
Standard chemotherapy combined with monoclonal antibody therapy
BTK inhibitors (with or without chemotherapy)
Stem cell transplantation (for select patients)
Maintenance therapy with monoclonal antibodies or targeted oral therapies
Participation in clinical trials exploring new treatment combinations
The doctor may recommend any of the following methods for managing Mantle Cell Lymphoma
Watchful waiting/Active surveillance
For some patients with slow-growing mantle cell lymphoma who are otherwise in good health, doctors may recommend active surveillance or watchful waiting. The doctor will carefully monitor the cancer with regular screening and diagnostic tests. If the doctor detects any symptoms or signs of progression, he or she may recommend starting active treatment.
Chemotherapy
Chemotherapy is the use of drugs to treat rapidly growing cancer cells in an effort to
destroy them. Chemotherapy medications may be given through the vein (intravenously) or by mouth (orally).
Chemotherapy combined with monoclonal antibody therapy is the most commonly prescribed treatment for mantle cell lymphoma. Doctors may also recommend high-dose chemotherapy with stem cell transplantation as a part of initial therapy for patients with mantle cell lymphoma. When this is recommended, it is after patients have received chemotherapy in combination with immunotherapy and possibly oral targeted therapy and the lymphoma has responded to that treatment. There are several different types of chemotherapy drugs that can be combined for the treatment of mantle cell lymphoma.
Monoclonal Antibody Therapy
Monoclonal antibody therapy involves the use of specialized drugs, called antibodies, that function like components of the immune system to attack cancer cells. These medicines are similar to the antibodies naturally produced by the body’s B cells, which help fight infections by targeting bacteria and other harmful agents. However, monoclonal antibodies in cancer treatment are designed to specifically recognize and bind to certain markers on lymphoma cells, triggering their destruction.
In mantle cell lymphoma (MCL), monoclonal antibody therapy is commonly used in combination with chemotherapy, and it may also be recommended alongside oral targeted therapies or as maintenance therapy after initial treatment.
Key Monoclonal Antibodies in MCL Treatment:
Rituximab (anti-CD20) – The most frequently used monoclonal antibody for MCL, rituximab targets the CD20 protein on B cells, aiding in their elimination.
Obinutuzumab (anti-CD20) – Another CD20-targeting antibody that has been studied for its role in MCL treatment.
CD19-targeting antibodies – Currently under investigation for their potential effectiveness in MCL therapy.
Radiation Therapy
Radiation therapy uses waves of high-energy produced in a precise way from a machine to destroy lymphoma cells that are found in nodes or tumor masses. The doctor may recommend radiation after completion of chemotherapy to kill any mantle cell lymphoma that may be left over after the chemotherapy, especially if the disease is localized to only one part of the body. A doctor who gives these kinds of treatments is called a radiation therapist, or radiation oncologist. These doctors commonly use a radiation technique called involved-field radiotherapy to treat lymphomas. This technique allows them to target only the area of the body where the lymphoma is located.
Proton beam radiation therapy
Proton therapy is an advanced type of radiation therapy that uses “protons” rather than X-ray “photons” to deliver radiation to the tumor. In conventional radiotherapy, the photon beams can deposit radiation and damage healthy cells as they pass through the body. Proton therapy deposits most of the radiation directly at the tumor site, resulting in less damage to healthy tissue and fewer side-effects.
- Please see Understanding Proton Therapy to learn more.
Stem-cell Transplantation
This procedure allows patients to receive large doses of chemotherapy. High doses destroy lymphoma cells in the patient's body, but also cause significant damage to normal cells in the bone marrow. After chemotherapy, the patient receives blood-forming stem cells that help the body form new, healthy blood cells in the bone marrow. In an autologous stem cell transplant, the stem cells are collected from the patient prior to the administration of high dose therapy. In an allogeneic transplant, stem cells are collected from a healthy donor.
Protein Inhibitors
Protein inhibitors play a crucial role in disrupting tumor growth by blocking key proteins necessary for cell proliferation and the formation of new blood vessels. These targeted therapies hold significant promise for patients with lymphomas.
Various protein and small-molecule inhibitors, commonly referred to as “targeted therapies,” have been approved for relapsed or refractory lymphomas. Some have also gained approval for initial (frontline) treatment, while many others are being studied in combination with other therapies.
One major class of targeted therapies includes Bruton’s tyrosine kinase (BTK)inhibitors, such as acalabrutinib, zanubrutinib, and pirtobrutinib, which are approved for relapsed or refractory mantle cell lymphoma (MCL). Additionally, acalabrutinib is approved for frontline treatment when combined with monoclonal antibody therapy and chemotherapy.
Another key inhibitor, bortezomib, targets the NF-kB pathway and is available in intravenous and subcutaneous forms. It is approved for relapsed/refractory MCL and is also used in combination with chemotherapy for frontline treatment.
Venetoclax, an oral therapy targeting the BCL2 protein, has shown promising activity in multiple studies on MCL, although it is not yet FDA-approved for this indication.
Evolving Role in Treatment
Recent research suggests that these therapies—many of which are rapidly gaining FDA approval—may be as effective as standard, more intensive treatments for MCL. BTK inhibitors are already established as standard therapy when MCL relapses, and one oral BTK inhibitor is approved in combination with chemotherapy and monoclonal antibodies for initial treatment.
Ongoing studies continue to explore the benefits of these targeted therapies when used:
In combination with antibody therapy or chemotherapy
Alongside other targeted therapies
As maintenance therapy for initial MCL treatment
Several clinical trials have already demonstrated their potential as an effective initial treatment option when used in combination or as maintenance therapy for MCL.
Immunomodulators
Immunomodulators stimulate the patient's immune system to help it fight off lymphoma cells, but also have other ways to control the growth of cancer cells. These medications are also promising for therapy of lymphomas, especially mantle cell lymphomas, and the FDA has approved this type of medication for patients with mantle cell lymphoma who have relapse of their lymphoma. Studies have also shown it to be effective in combination with other therapies for initial treatment.
Lenalidomide is the currently approved immunomodulator therapy.
CAR-T Immunotherapy
One approach to immunotherapy approved for the treatment of mantle cell lymphoma at relapse involves engineering a patient’s own immune cells to recognize and attack their tumors. T-cells are a type of immune cell collected from the patient’s own blood. After collection, the T-cells are genetically engineered to produce special receptors on their surface called chimeric antigen receptors (CARs). These genetically engineered cells are then re-infused into the patient’s bloodstream. After re-infusion, the T-cells multiply in the patient’s body and with guidance from their engineered receptor, are able to recognize and kill cancer cells. The approved product (brexucabtagene autoleucel) targets CD19. In addition to the product that is approved, other products are being studied including others targeting CD19 and ones targeting other proteins.
Antibody Drug Conjugates
Antibody drug conjugates are antibodies linked to a “payload” or chemo-type drug that is delivered more directly to the cancer cell. There are none currently approved for mantle cell lymphoma but there are several approved for other non-Hodgkin lymphomas that are being studied in mantle cell lymphoma.
Bispecific Antibodies
Bispecific antibodies, or bispecific T cell engagers, are a form of immunotherapy. They are antibodies that target two types of cells (proteins or antigens), one on the cancer cell (lymphoma cell) and one on the T cell. These drugs have been shown in small clinical trials to be very active in mantle cell lymphoma and have been approved in other non-Hodgkin lymphomas. The bispecific antibody that has shown the most activity in mantle cell lymphoma targets CD20 on the B cell and CD3 on the T cell (glofitamab-gxbm) and is currently in a large clinical trial.
Clinical Trials
Clinical trials are studies of new cancer treatments that have promise in treatment of the disease. Phase 1 clinical trials introduce a new treatment to a small group of patients to determine if it is safe. Phase 2 clinical trials test if a specific type of cancer responds well to a new treatment or new combination of treatments. Phase 3 clinical trials usually compare a new treatment to a standard treatment for the disease. Such trials, particularly phase 2 and 3 trials, are designed to offer
the best chance of remission using standard or non-standard medications. These trials also answer important questions about how well these medicines work for the particular lymphoma being treated, and whether or not they are a good choice of treatment for patients with lymphoma. Such trials may also be the best treatment option for patients with lymphomas that have not responded well to traditional treatments.
