Mantle Cell Lymphoma

Mantle cell lymphoma explained briefly

Mantle cell lymphoma (MCL) is a rare form of blood cancer that, like many other lymphomas, develops from the so-called B cells of the immune system. These B cells, which are normally responsible for fighting off infections, develop uncontrollably in the case of mantle cell lymphoma and accumulate in the lymph nodes, bone marrow and other tissues.

What exactly is mantle cell lymphoma?

Mantle cell lymphoma belongs to the non-Hodgkin lymphomas and is characterised by a genetic change (a translocation between chromosome 11 and 14). This change leads to the overproduction of a protein called cyclin D1, which promotes cell growth. MCL usually affects people of middle to older age, more often men than women. Although it is considered an aggressive lymphoma, the development of the disease can vary from person to person.

Why do I have mantle cell lymphoma?

The exact cause of mantle cell lymphoma is not fully understood. However, there are some factors that can increase the risk:

• Age: Most cases occur in people over 60 years of age.
• Sex: Men develop the disease more often than women.
• Environmental factors: Contact with certain chemicals or radiation may possibly play a role.
• Genetic changes: As mentioned, the genetic change involving cyclin D1 plays a key role.

Symptoms of mantle cell lymphoma

In the beginning, mantle cell lymphoma may show no symptoms or only non-specific ones. Common signs are:

• Swollen lymph nodes (often painless)
• Tiredness and general weakness
• Unintentional weight loss
• Night sweats
• Fever with no identifiable cause
• Digestive problems (due to involvement of the gastrointestinal tract)

When is mantle cell lymphoma treated?

The decision to treat depends on the stage of the disease and the patient's general state of health. In early and slowly progressing stages, a wait-and-see strategy (“watch and wait") can sometimes be used. In more aggressive cases, however, immediate therapy is necessary.

How is mantle cell lymphoma treated?

The treatment of mantle cell lymphoma often combines different approaches, including:

• Chemotherapy: Frequently in combination with immunotherapies.
• Immunotherapy: Medications such as rituximab that specifically attack cancer cells.
• Targeted therapies: For example BTK inhibitors such as ibrutinib, which block signalling pathways in cancer cells.
• Stem cell transplantation: For younger and fitter patients, especially after successful initial therapy.
• Clinical trials: New treatment approaches are constantly being tested to improve therapy.

How exactly have clinical trials changed the treatment landscape in mantle cell lymphoma?

The TRIANGLE trial is a study by the European Mantle Cell Lymphoma Network. It investigated in patients with mantle cell lymphoma whether combining a targeted therapy with ibrutinib is just as good as or better than the classic treatment with stem cell transplantation.

Three groups were compared: standard therapy with stem cell transplantation, a combination of stem cell transplantation and ibrutinib, and a modern therapy with ibrutinib without stem cell transplantation.

The results showed that ibrutinib in combination with chemotherapy was more effective than the classic standard therapy with stem cell transplantation, especially in preventing disease progression. In some patients, the stem cell transplantation could be replaced by modern therapies such as ibrutinib, which makes the treatment less burdensome. Side effects occurred more frequently with the ibrutinib therapy, but were mostly manageable; the combination with stem cell transplantation in particular led to more side effects.

This study suggests that modern targeted therapies such as ibrutinib could in future represent an important part of the treatment of mantle cell lymphomas and can often replace the stem cell transplantation.

Dreyling, M., Doorduijn, J., Giné, E., et al. (2024). “Ibrutinib combined with immunochemotherapy with or without autologous stem-cell transplantation versus immunochemotherapy and autologous stem-cell transplantation in previously untreated patients with mantle cell lymphoma (TRIANGLE): a three-arm, randomised, open-label, phase 3 superiority trial of the European Mantle Cell Lymphoma Network." The Lancet, Volume 403, May 25, 2024, Pages 2293–2306. https://doi.org/10.1016/S0140-6736(24)00184-3