Skoronski Chair of Lymphoma Research at the University of Wisconsin School of Medicine and Public Health and Associate Director of Clinical Research at the UW Carbone Cancer Center
What is the standard maintenance therapy treatment for patients with MCL?
There is not necessarily a standard treatment because approaches can vary from institution to institution and from physician to physician. If maintenance therapy is used, it is typically with the drug rituximab, which is an anti-CD20 monoclonal antibody given as an intravenous infusion and typically given as a single dose every 2 months.
Data supports the use of maintenance rituximab therapy in patients with MCL over the age of 60. Tthis study, published in the New England Jounal of Medicine, patients who received R-CHOP and then went on to receive rituximab maintenance therapy (given as a single dose every 2 months indefinitely) stayed in remission longer than the patients who received R CHOP and interferon maintenance therapy.
We don't know if maintenanence rituximab can produce the same kind of benefit in younger patients, who receive a so-called "intensive regimen" as part of their induction therapy. A lot of younger patients will receive an intensive regimen like hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) or they will receive a stem cell transplant as part of their primary therapy. However, there isn't good quality data to support maintenance therapy in that group of patients.
What are some of the benefits of maintenance therapy?
A successful maintenance therapy helps the disease stay in remission longer. We generally think of MCL as an incurable neoplasm because it recurs in most patients. Once the patient is in remission, there is obviously a strong desire to have that remission last as long as possible. At the same time, it's important that any maintenance strategy have minimal toxicity since the maintenance therapies tend to be used for a long period of time. A maintenance therapy that helps people stay in remission longer, but has a lot of toxicity, could result in a diminished quality of life for that patient, which might not be a good tradeoff for a patient. So, it is very important for a maintenance therapy to be well tolerated, which is one of the really nice things about using rituximab as a maintenance therapy. For the vast majority of patients with MCL, it's a very well-tolerated treatment.
There are ongoing studies looking at the use of lenalidomide as a maintenance strategy in MCL, but we don't have long term data yet to support its use in routine practice. There are also studies that are looking at the combination of rituximab and lenalidomide together as a maintenance strategy; but, again, those studies are still underway and there isn't enough data to recommend that treatment strategy as part of routine practice yet.
Are there any other concerns, besides toxicity, that are considered when thinking about a maintenance therapy?
First, it needs to result in better disease control. The maintenance therapy has to do something useful. Secondly, the toxicity profile needs to be favorable. A theoretical concern about maintenance therapy is that it might promote the development of resistance, that is, mantle cells that are more resistant to treatment, although to date there is no evidence of that occurring.
Also, I think for a maintenance strategy to be useful, it needs to be patient-friendly. For example, if a maintenance strategy required the patient to come to the clinic twice a week for a 4-hour infusion for months and months, that wouldn't be considered very patient-friendly. That is too much time in the doctor's office and not enough time with family and friends.
Are there any other new maintenance therapies or treatments on the horizon that may be promising other than those you mentioned previously?
Ibrutinib was approved for MCL in November 2013, which is one of the more exciting new agents that has ever come along for MCL. I am expecting to see a whole series of trials designed to test ibrutinib as a maintenance strategy in MCL. There isn't sufficient data yet on the use of ibrutinib as a maintenance strategy, but I predict that a substantial amount of data will be generated over the next five years. We might find that ibrutinib turns out to be an excellent maintenance strategy for MCL. Ibrutinib is an oral agent, which makes it convenient for patients, and it has a good toxicity profile.
How did you become involved with the Lymphoma Research Foundation, and why would you recommend patients become involved with the organization?
The Lymphoma Research Foundation (LRF) is one of the few national organizations devoted to raising money to fund research to find better ways to treat lymphoma. As a lymphoma physician and a lymphoma investigator, I was naturally drawn to this organization, which benefits both me and my patients.
I think LRF is a wonderful organization. Not only do they do great work for patients, but they also do great work for physicians and the field of research with the research opportunities they provide. Needless to say, I am a huge fan of LRF. I'm a member of their Scientific Advisory Board and their Mantle Cell Consortium, and I view both as labors of love. The Mantle Cell Consortium provides opportunities for lymphoma researchers from around the world to get together, share information, talk about new advances, and design new strategies to make further advances in MCL.
Is there anything else that you'd like to add?
We are always trying to become more knowledgeable about MCL and its treatment options. Patient participation in clinical trials is very important. Clinical trials help develop new knowledge that benefits all patients with MCL. Physician and patient support in clinical research is crucial in advancing the field.