A Conversation About Mantle Cell Lymphoma with Dr. Michael Williams
Professor of Medicine, University of Virginia School of Medicine
Briefly describe Mantle Cell Lymphoma.
Mantle cell lymphoma (MCL) is one of the many subtypes of non-Hodgkin lymphoma (NHL). It comprises five to six percent of all NHL cases seen in North America, which translates to about four thousand new cases per year in the United States.
MCL was first recognized as a distinct clinical entity twenty years ago. Since then, there has been an effort to better understand this particular type of lymphoma and what makes it similar to or different from other NHL types, as well as an effort to improve therapies, which until recent years were not as effective as they were for other lymphoma types.
How is MCL typically treated?
Treatment varies depending upon a variety of factors; two of the most important are the patient’s age and his/her overall medical condition. Patients who are younger and relatively healthy will have more aggressive forms of treatment, typically with combination chemotherapy plus a monoclonal antibody like rituximab (Rituxan). Patients who are older or less healthy will typically be treated with lower intensity regimens.
A small subset of patients, perhaps twenty percent or so, may have a low tumor burden and be relatively asymptomatic. These patients can be observed for a period of time without any treatment, and have treatment initiated when symptoms appear or disease progression occurs.
What are the current main areas of research for MCL?
There is a great deal of exciting research going on with MCL. We are learning new information about the molecular and cellular biology of the disease, including what leads to MCL development and why some MCL cases are resistant or sensitive to certain treatments. We are increasingly identifying important molecular pathways that the MCL cells depend upon for survival; if you can block these pathways, then you may create new approaches to provide targeted therapy.
There is also exciting clinical research, including many studies supported by the Lymphoma Research Foundation (LRF), to help advance both the understanding of the disease and the development of new therapies.
Two important clinical studies from the European MCL network were recently reported, showing improved ways to treat previously untreated patients. They include the use of high-dose cytarabine (ara-C) regimens prior to hematopoietic stem cell transplants for younger and healthier patients, and the use of rituximab as long-term, maintenance treatment following initial treatment with rituximab plus chemotherapy.
For patients with relapsed disease, there are now a number of new, effective, and highly active treatment approaches that are providing a better quality of life and improved survival for people with MCL.
What are some of these new treatments for MCL?
Bortezomib (Velcade) is already approved in the United States for treating patients with relapsed MCL. Bendamustine (Treanda) has been used for people with both relapsed disease and with previously untreated MCL, usually in combination with rituximab. It is showing very high response rates and generally very good patient tolerance in terms of side effects. Lenalidomide (Revlimid) has activity in patients with relapsed disease, and is also being tested as maintenance treatment after initial therapy.
There are also several targeted therapies being tested, two of which have received a lot of attention recently: PCI-32765, an inhibitor of the Bruton's Tyrosine Kinase (BTK) protein; and CAL-101, which inhibits an enzyme called phosphatidylinositol-3-kinase (PI3K). Both drugs target different components of signaling pathways used by MCL cells that are very important for tumor cell survival. We are very encouraged by early reports and are looking forward to more mature data as studies continue.
When you discuss treatment options with patients, do you also discuss clinical trials?
Yes. Clinical trials are an exceedingly important component of disease management. The progress we’ve experienced with MCL treatment so far has come about due to active participation in clinical trials. Despite the progress we have seen and a number of very good current treatment options, we do not yet have a true standard of care for patients with the disease, so additional clinical trials are essential. Finally, clinical trials are often the best option for patients to get access to potentially effective new drugs. In fact the LRF provides a Clinical Trials Information Service to increase awareness about investigational treatments for lymphoma being evaluated at cancer treatment centers nationwide.
Can you describe your involvement with LRF?
I’ve been a member of the LRF Scientific Advisory Board for many years, and am actively involved with the MCL research effort, both as a former research grant awardee and as a current member of the Executive Committee of the MCL Consortium, which I chaired from 2005 until 2010. The LRF MCL Consortium holds an annual Workshop (this year will be the 9th Workshop) where approximately 80 investigators from North America and Europe can interact, build collaborations, and present their most recent research into MCL. The Workshop provides a stimulating forum for new research directions that will continue the progress in understanding MCL at the molecular and cellular levels, providing better treatment and, eventually, cure MCL.
Would you recommend that patients with MCL become involved with the LRF?
Yes. The LRF is the leading non-governmental funder of research in MCL. Many of the leading investigators in the US, Canada, and European Union participate with the MCL Consortium. LRF continues to fund grants supporting MCL research, and through its website and education programs they provide state-of-the-art information about MCL and other lymphomas. I routinely refer my patients to the LRF general website and their new disease-specific Focus On Mantle Cell Lymphoma site to find information about their disease and what they can expect from it. There is a lot of confusing information on the Internet, so having a resource like the LRF is quite useful for patients and their families.
Updated: February 15, 2012