Director of the Lymphoid Malignancy Program at the Cleveland Clinic
Can you briefly describe mantle cell lymphoma?
Mantle cell lymphoma (MCL) is a relatively uncommon type of lymphoma that accounts for about five to 10 percent of all non-Hodgkin lymphomas. MCL has characteristic biology and is almost always associated with expression of the protein cyclin D1, which is how the disease is defined. Using this and certain other tests, pathologists can identify these cancer cells under a microscope as MCL cells and distinguish this disease from other types of non-Hodgkin lymphomas.
MCL tends to occur more frequently in older adults; the average age of patients at diagnosis is between 60 and 70 years. It is three or four times more common in men than in women, so 75 to 80 percent of the patients are men.
What are the symptoms of MCL?
MCL presents a lot like other lymphomas. Many people have an enlarged lymph node in the neck, groin, or under the arm as with any lymphoma. Symptoms may also include fatigue, fevers, night sweats, and weight loss, but these are not specific for lymphoma or MCL.
What makes MCL different from other lymphomas?
MCL is more commonly seen in places outside the lymph nodes than other types of lymphoma. It is also very common for patients with MCL to have an enlarged spleen. The bone marrow and parts of the gastrointestinal tract, particularly the colon, are almost always involved, although symptoms are usually not present.
Can you discuss treatment options for MCL?
MCL tends to be faster growing than other indolent lymphomas, sometimes necessitating a more aggressive form of treatment. Because of this, people think that it needs to be treated right away. This is true for many people, but there are a significant number of patients, between ten and 20 percent, who have a more indolent, or slow-growing, form of the disease and may not need treatment for a long time.
If a patient does need treatment we evaluate whether they are a candidate for more intensive treatments or not. If the patient is not a candidate for more intensive therapy, we would use a combination of rituximab (Rituxan) and bendamustine (Treanda) (R-bendamustine), which is probably the most common treatment, often followed by maintenance therapy with rituximab alone. If they are a candidate for intensive therapy, most doctors would use a combination chemotherapy regimen followed by an autologous stem cell transplant to try to get a prolonged remission. Of course, taking part in a clinical trial is a way to ensure getting state-of-the-art treatment and helping advance knowledge about MCL.
Disease relapse is common. Until recently, treatment at relapse was either additional chemotherapy or bortezomib (Velcade) therapy but now we also have approved treatment with lenalidomide (Revlimid) and ibrutinib (Imbruvica).
What do you envision as future treatment options for MCL?
Building on treatments that were available when the trial was designed, in the US Intergroup Trial, an ongoing trial of which I am the principal investigator, we are investigating whether adding bortezomib (Velcade) to R-bendamustine improves outcomes. We are also investigating maintenance treatment and whether adding lenalidomide to rituximab during the maintenance period is beneficial for patients.
There was also a large randomized trial recently reported where vincristine, the O in R-CHOP, was replaced with bortezomib. This trial clearly showed that patients who received
bortezomib instead of vincristine experienced a longer progression-free survival.
With relapsed disease, we now have three approved options that are not traditional chemotherapy: bortezomib, ibrutinib or lenalidomide, often with rituximab . How to choose the best one for an individual patient will require more research on which patients are likely to respond to which drug. We also have some new options that are coming down the pipeline. ABT-199 is another oral agent that promotes cell death. ABT-199 is also being studied in chronic lymphocytic leukemia and other cancers. We know it is a pretty well-tolerated drug, and it appears active in MCL. Ibrutinib interrupts the signals that tell the cell to grow, while ABT-199 interrupts the signals that tell a cell not to die, so this is one rational combination to study. There are a number of additional oral drugs also being studied. I think the future lies in designing, and testing in clinical trials, combinations of these non-chemotherapy agents with the goal of controlling, or even curing, MCL with these designer drugs that are effective and have fewer side effects.
Can you discuss what patients with MCL can do to improve their treatment outcomes?
Ideally we hope to get a period of a few years where a patient does not have the disease and can live their life normally. We are always concerned about the risk of infection because a lymphoma patient’s immune system is not one hundred percent as a result of the disease itself and having had chemotherapy and rituximab. It is not necessary for patients to become hermits or to make a major lifestyle change, but they should use common sense to limit their risk of infections, such as washing their hands thoroughly and avoiding crowds. It is also important to eat right, get enough sleep, and exercise in order to strengthen the immune system.
What is your involvement with the Lymphoma Research Foundation and why would you recommend that patients become involved with the organization?
The Lymphoma Research Foundation (LRF) developed the Mantle Cell Lymphoma Consortium which has had a major role in fostering a research community that focuses on MCL, which has
really shown in the progress that we have had in this disease over the past few years. LRF has been a really important forum for disseminating research, communicating research, and keeping a group of researchers interested in lymphoma and MCL in particular. For me professionally, having these resources has been very important for developing basic scientific and translational research, and designing clinical trials. I don't think we would be where we are today without this research community that LRF developed.
It is important for patients to become involved with the Lymphoma Research Foundation because research costs money and we need patient advocates to try to help raise money and awareness to keep this disease on the forefront of research.