Chief, CLL Research and Treatment Program, North Shore-Long Island Jewish Medical Center
Please briefly describe chronic lymphocytic leukemia.
Chronic lymphocytic leukemia (CLL) is a cancer involving abnormal lymphocytes, or white blood cells, that remain alive far longer than normal lymphocytes. As a result, these cells accumulate in the body. CLL is therefore an accumulative rather than a proliferative cancer. The result of this accumulation is compromised bone marrow function, and consequently a decrease in platelets, an increase in infections, and enlarged lymph nodes and spleen.
How common is CLL?
CLL is relatively rare compared to, for example, lung cancer and breast cancer. Approximately six out of every 100,000 people in the United States are diagnosed with CLL each year.
How is CLL typically treated?
Fifty years ago, CLL was typically treated with chlorambucil (Leukeran), an alkylating agent. Chlorambucil is no longer commonly used in the United States. About 25 years ago, fludarabine (Fludara) was introduced as a treatment for CLL, and was eventually used in combination with cyclophosphamide (Cytoxan). Once the monoclonal antibody rituximab (Rituxan) became available approximately 15 years ago, it was combined with cyclophosphamide and fludarabine, and this three-drug combination (FCR) became the standard of care in CLL. Pentostatin (Nipent) has been used in place of fludarabine in this combination, and more recently bendamustine (Treanda) has become increasingly used in combination with rituximab (BR). Additional monoclonal antibodies are approved and used for CLL treatment, such as alemtuzumab (Campath) and ofatumumab (Arzerra); another treatment used is radioimmunotherapy with ibritumomab tiuxetan (Zevalin) and tositumomab (Bexxar), which are monoclonal antibodies linked to radioactive molecules.
What are the main areas of research for CLL?
Many drugs are being tested in CLL. Lenalidomide (Revlimid), an immunomodulatory drug approved in multiple myeloma (MM) and myelodysplastic syndromes (MDS), has shown promise. Lenalidomide (at a lower dose than that used for MM and MDS) is also being studied in combination with either rituximab or with ofatumumab, both in the upfront and relapsed setting. Another exciting new drug is GS-1101 (formerly CAL-101), belonging to a class of drugs called, "phospoinositide-3 kinase (PI3K) inhibitors," which inhibit the B-cell receptor (BCR). Bruton’s tyrosine kinase (BTK) inhibitors also inhibit the BCR and are being studied in CLL, and there are many other examples of BCR inhibition being studied.
Researchers are currently researching a CLL treatment involving the removal of immune system cells called, "T-cells" from heavily pre-treated patients, manipulating these T-cells to make them recognize and attack leukemia cells, and adding these back into the body of CLL patients. The process appears promising as a means to make the immune system target cancer cells.
Do you talk with your patients about enrolling in a clinical trial?
Yes, I always talk to my patients about clinical trials. Clinical trials are essential for progress in cancer research. I focus on communicating to and educating patients about clinical trials so they can make an informed choice about whether a clinical trial is suitable for their disease.
How are you involved with the Lymphoma Research Foundation (LRF)?
Would you recommend to a patient that they become involved with LRF?
Yes. LRF is an important forum for educating patients and the public about lymphomas and CLL. LRF has supported important research in these diseases and it also provides essential support for people with lymphoma and their families.