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Chronic Lymphocytic Leukemia: Emerging Therapies

Nonpharmacological Approaches

Chronic Lymphocytic Leukemia: Emerging TherapiesCurrently, the only potentially curative option for chronic lymphocytic leukemia is stem-cell transplantation, which is still a highly experimental approach. There are two main types of stem-cell transplantation: autologous, in which the patient’s own stem cells are harvested and then returned to his or her body, and allogeneic, in which a related or unrelated donor is the source of stem cells.

Allogeneic stem-cell transplantation carries the risk of the patient developing graft-versus-host disease, a condition in which the donated stem cells trigger an immune response against the patient. This complication can be fatal; indeed, allogeneic stem-cell transplantation carries a high risk of mortality. However, allogeneic stem-cell transplantation also provides a higher chance of cure, partly because of the graft-versus-leukemia effect, where by the donor’s stem cells trigger an immune response against the patient’s own leukemia cells.

There is no risk of graft-versus-host disease in autologous stem-cell transplantation, but neither does the beneficial graft-versus-leukemia occur. Another disadvantage of autologous stem-cell transplantation is that harvested and donated stem cells may be contaminated with tumor cells, which are then returned to the patient. The relapse rate for patients treated with autologous stem-cell transplantation is high.

Current research is investigating allogeneic stem-cell transplantation in a nonmyeloablative, rather than fully ablative, setting. Nonmyeloablative stem-cell transplantation uses less intensive conditioning regimens that rely on immunosuppression rather than cytotoxicity. In general, stem-cell transplantation is used in a minority of patients who are young and have poor prognostic factors or as a last-chance option for patients with advanced disease.

Emerging Therapies

The emerging therapy market for B-cell chronic lymphocytic leukemia (chronic lymphocytic leukemia) is extremely sparse. Only two agents are in Phase III development, and of the agents in Phase II development, data are available on only a minority. Further, progress on agents such as Novartis’s protein kinase inhibitor midostaurin (PKC412) and Bioenvision/Ilex’s antimetabolite clofarabine (Clofarex) has not been published. Two immunotherapeutic approaches are in Phase II development for chronic lymphocytic leukemia: the University of Southampton in the United Kingdom is developing a DNA vaccine that produces anti-idiotype antibodies conjugated to tetanus toxin, and Immuno-Designed Molecules is developing IDM-4, a macrophage-activated killer-cell bispecific antibody.

No clinical data are available on either of these agents. The proteasome inhibitor bortezomib (Millennium’s Velcade) has been extremely successful in the treatment of multiple myeloma and is under investigation for non-Hodgkin’s lymphoma. However, clinical trial data demonstrating its effect in chronic lymphocytic leukemia have not been published. For now, the focus remains fixed on monoclonal antibodies (monoclonal antibodies) to improve both response and overall survival rates in chronic lymphocytic leukemia.

TABLE. Emerging Therapies in Development for Chronic Lymphocytic Leukemia summarizes drug therapies in development for chronic lymphocytic leukemia.

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