Strategies to Improve Treatment - Chronic Lymphocytic Leukemia

This content has been reviewed and approved by

Hagop M. Kantarjian, MD
Chairman & Professor, Leukemia Department
MD Anderson Cancer Center
University of Texas

The progress that has been made in the treatment of chronic lymphocytic leukemia (CLL) has resulted from the incorporation of new anticancer agents into treatment regimens and the performance of clinical trials. Future progress will result from continued participation in appropriate clinical trials. Currently, there are several areas of active exploration aimed at improving treatment.

Supportive care - Supportive care refers to treatments designed to prevent and control the side effects of cancer and its treatment. Side effects not only cause patients discomfort, but also may prevent the optimal delivery of therapy at its planned dose and schedule. To achieve optimal outcomes from treatment and improve quality of life, it is imperative that side effects resulting from cancer and its treatment are appropriately managed.

New chemotherapy regimens - Development of multidrug chemotherapy treatment regimens that incorporate new or additional anticancer therapies is an active area of clinical research. Fludara^® (fludarabine phosphate), Leustatin^® (cladribine), and Nipent^® (pentostatin) are all anticancer agents being evaluated alone or in combination.

Monoclonal antibodies - Monoclonal antibodies are proteins that can be made in the laboratory and are designed to recognize and bind to very specific cells. Monoclonal antibodies can locate cancer cells and kill them directly or stimulate the immune system to kill them, while sparing most healthy cells in the body from destruction.

This is in contrast to chemotherapy or radiation, which do not differentiate between cancer cells and healthy cells in the body, a characteristic leading to potentially destructive side effects. Monoclonal antibodies can be administered alone or before or after chemotherapy and are being evaluated in combination with chemotherapy to determine whether the combination can improve cure rates.

Rituxan^® (rituximab) is a monoclonal antibody that binds to proteins on the surface of B-lymphocytes. This binding action stimulates the immune system to attack and kill the cancerous B-cells. Rituxan produces anticancer responses in patients with advanced CLL; however, the duration of responses appears relatively short.

Campath^® (alemtuzumab) is another monoclonal antibody that binds to proteins on the surface of B- and T-lymphocytes.

(Revlimid^®) lenalidomide is a new drug with a new mechanism of action (immunomodulatory inhibitory derivative [IMID] of thalidomide). In two different studies, the drug has shown good activity in CLL after failure of fludarabine regimens.

Stem cell transplant - High-dose chemotherapy and allogeneic stem cell transplantation as treatment for CLL has been evaluated. Delivery of high-dose chemotherapy and allogeneic stem cell transplantation has been associated with a high mortality rate, with 20 percent to 40 percent of patients dying from complications of treatment within 2 years of transplantation. However, 50 percent to 80 percent of patients survive without evidence of recurrent CLL 3 or more years from treatment.

These results are encouraging and suggest patients with advanced CLL may be curable. Several technological changes have occurred since these patients were treated, which could reduce the mortality associated with this therapy. These technological changes, combined with using this therapy earlier in a patient's disease course, will hopefully have lower levels of toxicity. Further evaluation of high-dose chemotherapy and autologous or allogeneic stem cell transplantation as primary treatment for younger patients is ongoing.

Gene therapy - Gene therapy is defined as the transfer of new genetic material into a cell for therapeutic benefit. This can be accomplished by replacing or inactivating a dysfunctional gene or replacing or adding a functional gene into a cell to make it function normally. Gene therapy has been directed towards the control of rapid growth of cancer cells, control of cancer death, or efforts to make the immune system kill cancer cells.