Hope from Experts: Richter Transformation in Chronic Lymphocytic Leukemia

A Discussion About Richter Transformation in Chronic Lymphocytic Leukemia with Tanya Siddiqi, MD, City of Hope



How would you briefly describe chronic lymphocytic leukemia?

Chronic lymphocytic leukemia (CLL) is a type of slow-growing non-Hodgkin lymphoma. It is a cancer that arises from a patient’s own white blood cells, known as B lymphocytes. One of the cells becomes cancerous and starts making many more copies of itself. CLL is an indolent or low-grade type of cancer and is usually treatable. There are different ways to control the disease or even to achieve a remission (signs of lymphoma disappear after treatment), but we do not consider CLL a curable disease, per se. It is more of a long-lasting or chronic condition that comes and goes at various points throughout this journey.

How common is CLL?

CLL is one of the most common blood cancers in the western world. Approximately five out of every 100,000 persons in the United States are diagnosed with CLL each year. That means about 20,000 new cases of CLL will be diagnosed in the United States in 2017.

How is CLL typically treated?

There are several approaches that can be taken to treat CLL. Because CLL is a low-grade disease that is not curable, most of the time we do not begin treatment right away after the diagnosis is made. Often, we actively observe patients for several years before treatment is needed. This approach is also known as “active surveillance” or “watchful waiting” in which patients’ overall health and disease are monitored through regular checkup visits and various procedures, such as laboratory and imaging tests. Some patients never need treatment if they have a slowly progressing disease that does not change much over time. For patients who have more rapidly progressing disease and who are more symptomatic, there are certain guidelines that we use to determine the right time to begin treatment. Treatment options include chemotherapy, immunotherapy, combination therapy, or new targeted therapies. In recent years, there have been several new therapies approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with CLL, giving patients more treatment options than ever before, including a few targeted therapies that can be taken orally. These and several other therapies are being actively studied in clinical trials. I encourage patients to consider clinical trials so that they can receive the newest treatment, and so that we can learn more about these treatments for future generations. For more information on current treatments for CLL, please view the Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma fact sheet or Understanding Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma patient guide on the Lymphoma Research Foundation’s (LRF’s) website at www.lymphoma.org/publications.

Could you briefly describe Richter transformation?

Richter transformation occurs in less than 10 percent of cases of indolent lymphomas. It happens when CLL cells change or transform from indolent, small cells into large, more aggressive types. This transformation is harder to detect, because unfortunately this change cannot be diagnosed in its early stages the way we can diagnose CLL. Most commonly, CLL transforms into diffuse large B-cell lymphoma (DLBCL), which is a more aggressive non-Hodgkin lymphoma. Rarely, CLL can also transform into Hodgkin lymphoma or another type of aggressive lymphoma.

 What is the cause of Richter transformation?

We do not know the exact cause of Richter transformation. One theory is that there are many cells in the bodies of patients with lymphoma that already have the aggressive behavior, but they are somewhat hidden behind the actual CLL cells. Sometimes, these few aggressive cells become stronger and take over either the bone marrow, lymph nodes, or the whole body and become much more widespread, until they develop into a new type of lymphoma.

What is the typical course of treatment for CLL patients who develop Richter transformation?

When CLL transforms to a higher-grade lymphoma, we usually put patients on aggressive therapy right away. Historically, we used to try to control the disease with either combination chemotherapy, chemoimmunotherapy such as R-CHOP (the monoclonal antibody rituximab [Rituxan] added to combination chemotherapy [cyclophosphamide, doxorubicin, vincristine, prednisone]), or another aggressive regimen. In my experience, if patients have already been treated with rituximab, a different monoclonal antibody called obinutuzumab (Gazyva) may yield better results when added to a combination chemotherapy regimen like EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, hydroxydaunorubicin) or ICE (ifosfamide, carboplatin, etoposide).

There are some clinical trials now studying nonchemotherapeutic agents like monoclonal antibodies and combining them with targeted therapies like ibrutinib (Imbruvica). Although our combination chemotherapy approach is not ideal, it is often the best option for patients who are not eligible for a clinical trial. At first, we use several cycles of a combination chemoimmunotherapy to try to induce a remission. At that point, for patients who are eligible for allogeneic stem cell transplantation, we try a transplant to see if we can achieve a partial or even full remission.

What advice would you give to a newly diagnosed CLL patient?

I tell newly diagnosed patients to live as healthy and as normal a lifestyle as possible, because often people do not need treatment for many years. I also encourage patients to exercise, because that helps the immune system to fight.

Lastly, I tell them not to trust all the information they read or hear. Sometimes, well-intentioned family members and friends advise patients to take a supplement that will boost their immune system. The problem with that approach is that lymphoma arises from within the immune system, and we do not know whether taking herbal or traditional medicines that are immune boosters may actually help the cancer grow. Patients should definitely avoid taking any over-the-counter products that are intended to boost the immune system and should always talk to their healthcare team before trying anything new. I recommend patients connect with a reputable organization, like the Lymphoma Research Foundation to learn more about their type of lymphoma.

What advice would you give to a CLL patient who develops Richter transformation?

I would tell them to learn as much about Richter transformation as possible and to not be afraid of asking questions. When a Richter transformation occurs, the patient’s specific situation will determine which treatment option would be best for them. Often, a stem cell transplant is the most indicated treatment, and getting familiar with the risks and benefits of the transplantation process is important. LRF is an important source of information. I suggest downloading a copy of their Understanding the Stem Cell Transplantation Process publication because it is a very comprehensive guide that will help answer many questions that patients may initially have. LRF also offers numerous resources that answer questions related to various other treatment options, the latest in CLL research, and ways to cope with all aspects of the patient’s diagnosis. In addition, LRF provides educational in-person meetings, teleconferences, a peer support program, as well as a very helpful mobile app called Focus On Lymphoma (www.FocusOnLymphoma.org). All these resources will help patients with lymphoma be well connected to expert information and valuable support.

How are you involved with the Lymphoma Research Foundation, and why would you recommend that patients become involved with the Lymphoma Research Foundation?

I have given patient education presentations through the LRF in-person education programs. It is extremely rewarding to give patients a chance to ask their questions and to help them learn more about their disease.

It is very important that patients with CLL educate themselves about the latest treatments, the best diagnostic techniques, and follow-up options. I feel it is important for patients to get recommendations and advice from a cancer center where CLL is treated much more commonly and that have an expertise in CLL. The treatment field is changing so quickly that patients need to stay up to date and consider their long-term care. When patients are empowered with knowledge, they can advocate for themselves much better than anyone else can for them. LRF is a great resource for them to acquire this education and knowledge. I enjoy helping these patients by giving talks, because I think that it is very important for our patients to learn all they can so they can be their own advocate when navigating through their CLL diagnosis and treatment options.

Is there anything else that you would like to add?

I think clinical trials are key in CLL, because there are many new treatment options that are being tested. The faster we can get patients enrolled in trials and get the analyses done, the faster we can get FDA approval of new drugs for commercial use. That will bring more treatment options into the community for more patients. I encourage patients to consider clinical trials as their first option whenever they are ready to begin treatment.