Professor of Medicine, Georgetown Lombardi Comprehensive Cancer Center
Please briefly describe CLL.
Chronic lymphocytic leukemia (CLL) is a cancer of the immune system. It is an accumulation of abnormal lymphocytes, which are components of the immune system in the body; these lymphocytes accumulate in the bone marrow, the lymph nodes, the spleen, and, most notably, in the blood stream. CLL is often diagnosed accidentally at the time of some other medical investigation; a patient might, for example, be treated for a hernia repair and discover they have leukemia because they have a blood test and their lymphocyte count is elevated, and their lymphocytes have certain features characteristic of CLL.
CLL has a very heterogeneous clinical course. Many patients can go from months to years to decades without ever requiring therapy, whereas others need treatment fairly soon after the time of diagnosis. There are a number of biological, immunological, and genetic factors that can predict which patients are most likely to require therapy; but these are not uniformly reliable in that regard.
How common is CLL?
CLL is the most common form of leukemia in Western countries, with about 15,000 to 16,000 new cases a year. But since many patients live for a long time, there are hundreds of thousands of people living with CLL. Many of these people have no signs or symptoms of this disease and are living a normal life.
How is CLL typically treated?
The initial treatment for CLL is somewhat controversial. The combination of fludarabine, cyclophosphamide, and the monoclonal antibody rituximab (FCR) is probably the most popular regimen, but increasing in popularity is the combination of bendamustine and rituximab (BR). Other therapies available for this disease include ofatumumab, which is a monoclonal antibody somewhat similar to rituximab, and alemtuzumab, which is another monoclonal antibody. These are used primarily in the setting of patients whose disease has recurred after treatment with either FCR or BR or a similar regimen.
Currently, what are the main areas of research for CLL?
There are a number of important areas of research. We are still studying the genetics of CLL so that we can better understand why it does what it does. A condition called "monoclonal lymphocytosis of undetermined significance," or MLUS, can be found in a substantial proportion of the population, probably as high as five percent or maybe even higher, depending on the age group. We are looking at the relationship between MLUS and CLL, to see how many patients with this condition progress to CLL. Since CLL tends to run in families, investigators are also studying familial CLL.
Therapeutics is another important area of research. Although we use FCR or BR, CLL remains an incurable disease, and the majority of patients fail to achieve a complete remission. Several agents in development appear to have promise. Two of these in particular, CAL-101 and PCI-32765, are oral drugs called kinase inhibitors; these are very active in patients with relapsed and refractory CLL and are now being further developed in combination with other drugs. GA-101 is a monoclonal antibody that, like rituximab, targets a protein on the cell surface called CD20. GA-101 is being directly compared with rituximab in clinical trials. There are other antibodies targeting other proteins on the surface of CLL cells, such as CD19, and drug-antibody conjugates, in which the antibody is bound to a toxin. In addition, immunomodulatory drugs (IMiDs), such as lenalidomide, are active in CLL. Many more drugs are being evaluated.
We also need to improve on stem cell transplantation for CLL. For some patients, nonmyeloablative allogeneic transplants can be quite effective. However, there are toxicities associated with this approach, and we need to be able to improve efficacy while reducing toxicity.
When you speak to patients about treatment options, do you suggest clinical trials?
We always recommend a clinical trial if there is one available. As I mentioned, not all patients with CLL need treatment at diagnosis or ever need treatment, but when they do need treatment, or if they fail initial treatment, then our first recommendation should always be a clinical trial. A Clinical Trials Information Service is provided by LRF to increase awareness about investigational treatments for lymphoma..
How are you involved with the LRF and why would you recommend that a patient become involved with them?
I've been involved with the Lymphoma Research Foundation (LRF) for many years, even before it was the LRF. I have been on their Scientific Advisory Board, and I am currently the Chair. I also have done a lot of fundraising for the LRF. My wife and I organize a lymphoma/CLL patient bicycle ride, which has raised about $2 million for the LRF over five years. I have also participated in a number of live meeting sessions for the LRF, in which medical experts answer questions from patients and caregivers about hematologic malignancies in a town hall format, and I am the co-chair of this year's North American Educational Forum.
I think the LRF is an exceptional organization because not only does it fund high-quality research, but it is involved in patient education, and has a very strong advocacy presence. It is also involved in government relations, which is important for addressing hematologic malignancies and for helping patients with these diseases. Education, research,advocacy, and government relations are all important areas in which the LRF is involved. They also have an exceptional, newly revised website and disease-specific sites for patients to access information about CLL, follicular lymphoma,peripheral T-cell lymphoma, mantle cell lymphoma, Hodgkin lymphoma and anaplastic large cell lymphoma.