Treatment Options for Chronic Lymphocytic Leukemia

Monoclonal Antibody Immunotherapy in Chronic Lymphocytic Leukemia

Monoclonal antibodies are antibodies derived from a single clone of antibody producing B-lymphocytes that recognize and bind to only one specific antigen (such as the CD52 antigen or the CD20 antigen present on the surface of CLL cells). Monoclonal antibodies are produced in the laboratory by a special process (hybridoma technology) and administered to patients by either intravenous injection or infusion. Immunotherapy with monoclonal antibodies represents a more recent and novel approach for the treatment of chronic lymphocytic leukemia (CLL). When administered to the patient with CLL, monoclonal antibodies preferentially seek-out and bind to leukemic cells in the blood and bone marrow. The binding of the monoclonal antibody to specific cell surface markers (antigens) on leukemic cells triggers the patient's own immune system to recognize and destroy the leukemic cells. Examples of monoclonal antibodies that are used for the treatment of CLL include:

  • Alemtuzumab
  • Rituximab

Alemtuzumab

Alemtuzumab (Campath) is an anti-CD52 monoclonal antibody that recognizes and binds to the CD52 antigen that is present on almost all CLL cells. Alemtuzumab was initially approved by the U.S. Food and Drug Administration (FDA) in 2001 for the treatment of B-cell chronic lymphocytic leukemia that is refractory to treatment with alkylating agents and fludarabine.

In September 2007, the FDA granted regular approval and expanded labeling for alemtuzumab (Campath) as single-agent treatment for B-cell chronic lymphocytic leukemia. Alemtuzumab was initially approved in 2001 under accelerated approval regulations. Conversion to regular approval was based on a single multicenter, randomized clinical trial of 297 patients with previously untreated B-cell CLL who were experiencing progression of their disease. Patients in this study were randomized to either alemtuzumab or chlorambucil therapy. The progression-free survival time was significantly longer for the alemtuzumab-treated patients than for those who were treated with chlorambucil. Both the overall and complete response rates were also significantly higher in the alemtuzumab-treated group compared to the chlorambucil-treated group.

Common side-effects of alemtuzumab include:

  • Fatigue
  • Fever
  • Chills
  • Muscle aches
  • Allergic reactions
  • Dizziness
  • Headaches

Infrequent, but potentially serious, effects of alemtuzumab include:

  • Autoimmune hemolytic anemia
  • Thrombocytopenia
  • Severe infections

Rituximab

Rituximab (Rituxan) is an anti-CD20 monoclonal antibody that preferentially recognizes and binds to the CD20 antigen expressed by normal and malignant B cells (including B-cell chronic lymphocytic leukemia). Rituximab has been approved by the FDA for the treatment of Non-Hodgkin's lymphoma and is also being investigated as a potentially effective treatment for chronic lymphocytic leukemia. Studies have shown that rituximab is more effective for the treatment of CLL when it is used in combination with other drugs such as:

  • Fludarabine
  • Fludarabine plus cyclophosphamide
  • Pentostatin plus cyclophosphamide

Common side-effects of rituximab include:

  • Fever
  • Chills
  • Weakness
  • Nausea
  • Headache

Infrequent, but potentially serious, effects of rituximab include:

  • Kidney failure
  • Severe skin reactions
  • Congestion of the lungs
  • Abnormal heart rhythm
  • Low blood pressure

In 2004, Biogen Idec and Genentech notified healthcare professionals of revisions to the WARNINGS section of the prescribing information for Rituxan due to reports of Hepatitis B virus (HBV) reactivation with fulminant hepatitis, hepatic failure, and death in some patients with hematologic malignancies. Persons at high risk of HBV infection should be screened before initiation of Rituxan. Carriers of hepatitis B should be closely monitored for clinical and laboratory signs of active HBV infection and for signs of hepatitis during and for up to several months following Rituxan therapy.

Monoclonal Antibodies in Development

Currently, there are several monoclonal antibodies in development for the treatment of CLL. Examples include:

  • Epratuzumab - a humanized monoclonal antibody targeting the CD22 antigen on B-cells
  • Apolizumab - a humanized monoclonal antibody directed against the 1D10 antigen on B-cells
  • Lumiliximab - an anti-CD23 monoclonal antibody