Associate Member, Clinical Research Division, at Fred Hutchinson Cancer Research Center; Associate Professor, Medical Oncology Division, University of Washington School of Medicine
Would you briefly describe Chronic Lymphocytic Leukemia (CLL) and discuss how common it is?
Chronic lymphocytic leukemia, also known as CLL, is the most common leukemia. CLL is more common than acute leukemia such as acute myeloid leukemia or acute lymphoblastic leukemia, and also more common than the other chronic leukemia called chronic myeloid leukemia. CLL is is a disease primarily found in people who are older. Typically the median age is the mid- to late-60s, and it's commonly found and diagnosed incidentally in someone having a high white blood cell count.
CLL is a malignant disorder of clonal lymphocytes that don't die and proliferate. These malignant CLL cells are generated from the bone marrow and circulate out into the blood, and thus the white blood count gets too high. The diagnosis can be made relatively simply. These malignant cells can be seen by looking at the blood under the microscope and seeing too many of these lymphocytes. In addition, special tests such as flow cytometry can be performed to look at the characteristic pattern or signature that uniquely goes along with CLL, allowing for a relatively clear diagnosis in most cases.
Sometimes people can present with enlarged lymph nodes in their neck or under their arm. It's less common to present with more advanced disease where the spleen is enlarged or the red blood cell count or platelet counts are too low. Most of the time, people present in very early stages, feel perfectly fine, and are usually asymptomatic. People can often live with this disease for well over a decade or more. In fact, survival has been increasing and improving because of our new therapies. Currently, there are a lot of exciting therapies in development; however, importantly, when people present with CLL we don't do anything until they actually need treatment because of symptoms or rapidly progressive disease.
How is CLL typically treated and what chemotherapy regimens do your patients usually receive first?
It is important to note when people present in the early stage of disease, perhaps just with an elevated white blood cell count either with or without some lymph nodes that may be involved, we primarily don't do anything. We watch those patients until there's reason to initiate treatment, and could end up waiting years before treatment is needed.
When treatment is needed, there is an extensive list of treatment options available to suit individual patient needs, taking into account the patient's age, his/her performance status, what the treatment goals are, his/her ability to get back and forth to clinic, etc. The gold standard for treatment at this point has been a combination chemotherapeutic regimen with the antibody rituximab (Rituxan) known as FCR (fludarabine-cyclophosphamide-rituximab). That regimen has been effective for getting very high complete response rates and outstanding overall response rates that lead to very good, long-term median progression-free survivals of many years. It's a toxic regimen, however, and somewhat difficult to administer to older patients or to patients who are more medically infirm. Because of this, a regimen of bendamustine-rituximab has become very popular and there are a variety of other chemoimmunotherapeutic regimens that could be considered. The interesting thing is that many people who may be a bit older and not interested in getting chemotherapy are often interested in low toxicity kinds of targeted biologic therapies. In particular, people might receive antibody-based therapies; there are several that are reasonable.
I think the other important thing to note is that in this day and age, there are a lot of exciting new therapies that are really changing the way we treat CLL. We're really getting away from treating patients with chemotherapy. There are some new oral drugs and new targeted IV (intravenous) antibodies or antibody-like therapies that are also exciting. These therapies are changing the game, meaning we're getting away from using chemotherapy and, hopefully, will be able to turn CLL into disease such that people can hopefully go extensive periods of time before relapsing without receiving chemotherapy.
In some cases, more aggressive treatments are needed, such as stem cell transplantation. Allogeneic transplants in this disease can be curative, but stem cell transplantation comes with some risk. Currently, another very exciting field is the generation of T-cell directed therapies for patients with CLL that also might provide significant improvements in long-term survival for patients with very advanced disease.
Are T-cell directed therapies the main areas of research for CLL or are there others?
That's just one of the areas of research, and there are several other areas. There are several new drugs that target specific pathways in the B-lymphocyte or the CLL cell. There are molecules that interrupt the B-cell signaling cascade inside the CLL cell. An example of new and improved antibodies in development would be the anti-CD20 GA101 (obinutuzumab) antibody. There are a host of other new targets being explored, including CD37 targeted a drug called TRU-016.
Can you talk about the importance of clinical trials and are there any specific trials that you would like to discuss?
It's very difficult to make advancements without patient participation in and consideration of clinical trials. Virtually every advance we've made ultimately has been developed through clinical trials. The appeal of the clinical trial for patients with CLL is to get something new and novel that has the potential to change the natural history of their disease. For many patients, that type of opportunity or approach is extremely valuable. There are a handful of drugs in clinical trials right now that, if patients can get in the trial, may have extreme appeal over standard chemotherapy regimens. For example, there are oral drugs in clinical trials right now that are very exciting: ibrutinib, idelalisib, and ABT-199. These drugs appear to have a high degree of activity in patients with CLL that is associated with very low toxicity. Currently, you can only get these drugs in clinical trials and therefore, without participating in a clinical trial, patients are not going to have a chance to get these kinds of promising drugs at this time or others in the future.
What advice would you give to a newly diagnosed patient?
I think newly diagnosed patients need to know that a CLL diagnosis is not uncommon. They're commonly going to do well but they need to be followed closely. Patients need to be well educated on their disease and they should ask questions and feel comfortable with their care and when they do need treatment they should explore all treatment options. And, at every stage or every encounter where treatment might be needed, patients should consider participating in a clinical trial that might be right for them.
How are you involved with the Lymphoma Research Foundation (LRF) and why you would recommend a patient become involved with LRF?
The Lymphoma Research Foundation is an important organization. Their mission is to bring meaningful research opportunities and education directly to patients and I know they are highly effective at achieving their goals. The organization cares about patients with lymphoma and understands that these goals have to be met today. I was lucky enough to get a Career Development Award from the Lymphoma Research Foundation many years ago, which really was a springboard to developing my lymphoma research career, further developing the ability to do research, get grants, and translate meaningful therapies from the lab to the clinic for patients with CLL. The Lymphoma Research Foundation is an incredibly important organization and they do a great job.