Mantle cell lymphoma (MCL) is often an aggressive form of cancer traditionally treated with chemotherapy, immunotherapy, and stem cell transplants when appropriate. Emerging therapies may offer more targeted disease management.

Mantle cell lymphoma (MCL) is a type of B-cell non-Hodgkin lymphoma. It is a cancer originating in the lymphatic system, the network of lymph vessels, nodes, and organs responsible for supporting immune function and maintaining fluid balance in the body.

As a B-cell lymphoma, MCL develops out of specific B cells called mantle cells. Mantle cells make up the mantle layer of lymph follicles, structures found throughout lymph nodes and other lymphatic organs.

MCL is often aggressive and typically widespread by the time of diagnosis. First-line treatment traditionally involves chemotherapy, with immunotherapy and stem cell transplants (SCTs) used as combination or supportive therapies.

This article looks at the latest and emerging treatment options for MCL and how they offer new ways to manage this condition.

Mantle cell lymphoma is historically difficult to treat. It can present with varied symptom severity, may progress at different rates in different people, and has a tendency to relapse after initial treatment.

Differences in its underlying pathology can also make some MCL treatments effective for certain people but not for others.

While chemotherapy has been the long-time standard for MCL treatment, these clinical inconsistencies have created a need for more individualized therapies.


Immunotherapy uses a person’s own immune system to fight cancer cells by modifying certain functions or enhancing immune activity.

Bispecific T-cell engagers (BiTEs) and chimeric antigen receptor (CAR) T-cell therapy are two examples of evolving immunotherapy options for MCL.

BiTEs are engineered proteins that serve as a bridge between MCL cells and T cells, immune cells responsible for recognizing and neutralizing pathogens in the body.

BiTEs have the ability to simultaneously bind to specific antigens, or protein markers, on the surface of MCL cells as well as to T cells, essentially bringing the T cell to the MCL cell.

Examples of BiTEs include:

  • blinmarlimab
  • blinatumomab
  • AFM13

CAR T-cell therapy boosts the immune system itself, specifically T cells. T cells from a person with MCL are extracted and genetically modified to express chimeric antigen receptors (CARs) on their surface.

Once infused back into the body, the CAR on T cells binds to MCL-specific antigens, such as CD19, and initiates apoptosis, or cellular death.

Examples of CAR T-cell agents include:

  • brexucabtagene autoleucel
  • lisocabtagene maraleucel

Epigenetic agents

Substances that alter genetic expression are known as epigenetic agents. Because MCL is characterized by specific genetic alterations that contribute to its development, epigenetic agents for treatment are an area of clinical interest.

Epigenetic agents work to reverse the over-expression of the CCND1 gene in MCL due to genetic translocation. Translocation occurs when one piece of a chromosome breaks off its original location and attaches to another chromosome.

The genetic component of MCL is credited with the cancer’s aggressive nature and high rate of relapse.

Research from 2022 using epigenetic agents in MCL achieved better treatment outcomes than traditional chemotherapy regimes.

Examples of epigenetic agents include:

  • romidepsin
  • vorinostat

Molecular inhibitors

Molecular inhibitors are drugs that target specific molecules or molecular pathways critical to cancer progression.

Bruton’s tyrosine kinase (BTK) inhibitors, for example, block the activity of Bruton’s tyrosine kinase, an enzyme essential in B cell development and survival. By blocking BTK, the growth of cancerous B cells is repressed.

Molecular inhibitors in MCL all have different functions and interrupt cancer development in unique ways.

Molecular inhibitors showing promise in MCL therapy include:

  • BTK inhibitors
  • BCL-2 inhibitors
  • PI3K inhibitors
  • proteasome inhibitors

Monoclonal antibodies

Monoclonal antibodies (mAbs) are engineered immune cells that bind to MCL-specific surface antigens. By binding to the antigens, mAbs help the immune system recognize cancer cells as abnormal, triggering an immune response against them.

Examples of monoclonal antibodies include:

  • rituximab
  • obinutuzumab
  • alemtuzumab

Monoclonal antibodies can be chemically paired with chemotherapy drugs to create antibody-drug conjugates (ADCs). ADCs link to MCL-specific antigens in the same way as classic monoclonal antibodies, but instead of using the immune system to fight the cancer cell, ADCs deliver a toxic chemical to cause cell death.

Examples of ADCs include:

  • polatuzumab vedotin
  • brentuximab vedotin
  • loncastuximab tesirine

Chemotherapy-free regimes

Even with emerging options that focus on genetics, molecular pathways, and modification of the immune system, chemotherapy remains a cornerstone of MCL management.

Novel therapies, such as molecular inhibitors, are typically used in combination with chemotherapy to provide more comprehensive treatment.

Research continues to expand what experts know about MCL. By uncovering and understanding more about MCL’s pathology, treatments can grow beyond broad chemotherapy approaches into targeted, disease-specific therapies that potentially improve cancer outcomes.

Novel therapies offer a way to treat MCL across various presentations with individual factors, such as age and genetics, which may affect treatment success.

By definition, “cure” indicates certainty that cancer is completely gone and will never return. There is currently no cure for MCL, and it is impossible to know if a cure will be found in the future.

Long-term remission in MCL is possible, however. Remission can be full, where no symptoms or signs of cancer remain, or it can be partial, where cancer decreases but is not entirely gone.

As medical research advances MCL therapy, remission rates and survival may improve.

The symptoms of MCL vary from person to person. Many people present with non-painful lymph node swelling as their only complaint, while others might have classic “B symptoms,” a set of specific experiences associated with B cell dysfunction.

Emerging therapies that target specific disease pathways in MCL may also provide symptom relief by repairing physiological processes in the body.

Epigenetics, for example, helps restore baseline cellular function by regulating genetic expression. As certain functions in the body improve, the symptoms associated with them may also improve.

Mantle cell lymphoma is an aggressive form of B-cell non-Hodgkin lymphoma, a cancer of the lymphatic system. While traditionally treated with chemotherapy, the diversity of MCL presentations and lack of universal medication responsiveness have increased the need for more targeted therapies.

Immunotherapies, epigenetic agents, and molecular inhibitors are among a few of the emerging treatment options available for MCL.

By addressing underlying disease pathways, such as genetic expression, these therapies may also help improve MCL and its symptoms.