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Results recently presented at the 2005 annual meeting of the American Society of Clinical Oncology (ASCO) state that the radiotherapeutic agent Zevalin® (Yttrium 90 ibritumomab tiuxetan, or 90Y IT) is a safe and effective treatment option for non-Hodgkin’s lymphoma (NHL) patients who have received extensive prior therapy, including a stem cell transplant.

Non-Hodgkin’s Lymphoma (NHL) is a form of cancer that begins in the cells of the lymph system, which includes the spleen, thymus, tonsils, bone marrow, lymph nodes and circulating immune cells. Lymphocytes are the main cells in the lymph system and exist in two forms: B and T-cells. Each of these cells serves a specific function in aiding the body fight infection. In NHL an excessive amount of atypical (cancerous) lymphocytes accumulates in the lymph system. These lymphocytes can crowd and suppress the formation and function of other immune and blood cells. While NHL is categorized by the type of lymphocyte it involves, it is also further defined by the rate at which the cancer grows. The appearance of the cells under a microscope indicates the growth rate. High-grade or aggressive NHL is the fastest growing, whereas low-grade or indolent lymphoma develops slowest. Lymphoma that has returned following therapy is classified as recurrent; refractory lymphoma is cancer that has stopped responding to standard therapies.

The biological agent Zevalin is approved for treatment of recurrent or refractory indolent B-cell NHL. Zevalin uses two mechanisms to target and kill cancer cells. It is comprised of ibritumomab, a monoclonal antibody that is attached to a radioactive substance called Yttrium 90 (90Y). The monoclonal antibody portion of Zevalin binds to proteins (CD 20 antigen) found only on the surface of B-cells. When Zevalin binds to the cancer cells, the immune system is stimulated to attack the cancer cells while the attached 90Y destroys these cells by spontaneous radiation emission. Researchers speculate that Zevalin may also produce anticancer effects through additional mechanisms not fully understood at present. This type of treatment not only provides anticancer treatment through separate strategies, but also delivers greater amounts of radiation to the cancer cells than external radiation therapy. Additionally, radiation exposure to normal cells is minimized. Treatment with Zevalin includes initial administration of Rituxan® (rituximab), even in patients who have stopped responding to therapy with Rituxan alone. Rituxan is a monoclonal antibody that also binds to B-cells and is used commonly in the treatment of B-cell NHL.

A common approach in the treating NHL is a stem cell transplant. This involves high doses of therapy, followed by infusion of stem cells. Stem cells used in this process are immature blood cells that mature into one of three major types of blood cells once infused into the patient’s bloodstream. A stem cell infusion may be needed when high doses of therapy destroy a patient’s blood cells, leaving them susceptible to life-threatening infection, blood transfusions and bleeding. Unfortunately, once a patient experiences cancer progression or a cancer recurrence following a stem cell transplant, effective therapeutic options are limited.

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A recent clinical trial was conducted to evaluate Zevalin for the treatment of 10 patients with relapsed or refractory NHL. All patients had received prior treatment with a stem cell transplant, had undergone between three and seven prior treatment regimens and had stopped responding to treatment with Rituxan. Following treatment with Zevalin, half of the patients experienced anti-cancer responses, and detectable cancer disappeared in 20 percent of all patients. Side effects were limited to low levels of white blood cells and platelets.

Researchers concluded that treatment with Zevalin is an effective and safe treatment in patients with NHL who have undergone extensive prior therapy, including a stem cell transplant. Patients with refractory NHL may wish to speak with their physician regarding their individual risks and benefits of treatment with Zevalin.

Reference: Joyce J, Schuster M, McCook B, et al. Experience with Yttrium 90 Ibritumomab Tiuxetan (Zevalin®) After Autologous Stem Cell Transplant (ASCT) in Patients with Non-Hodgkin’s Lymphoma (NHL). Proceedings from the 2005 annual meeting of the American Society of Clinical Oncology. Abstract #6669.

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