According to a recent article published in the journal Blood, the use of high doses of Zevalin (yttrium-90-ibritumomab tiuxetan) in combination with high doses of chemotherapy appear very effective in patients with relapsed non-Hodgkin’s lymphoma.
Non-Hodgkin’s Lymphoma (NHL) is a form of cancer that begins in the cells of the lymph system (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.
Non-Hodgkin’s lymphoma is categorized by the type of lymphocyte it involves and 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. It uses a combination of mechanisms to target and kill cancer cells:
- Zevalin 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.
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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 is needed because high doses of therapy destroy a patient’s blood cells, leaving patients susceptible to life-threatening infection, blood transfusions, and bleeding.
Patients may also undergo full-body radiation as part of the treatment regimen for NHL. However, full-body radiation is associated with the development of secondary cancers, as well as extensive side effects. Methods to reduce the use of full-body radiation are continually researched.
Researchers from the City of Hope National Medical Center recently conducted a clinical trial to evaluate high doses of Zevalin plus high doses of chemotherapy prior to an autologous stem cell transplant in patients with NHL. This trial included 31 patients who had cancer progression or recurrence following prior therapy or were considered to have a poor prognosis following therapy. At nearly 2 years follow-up, treatment with Zevalin appeared to produce impressive long-term results in these patients:
- 24 patients have maintained a complete disappearance of their disease (complete remission).
- Relapse-free survival is 78%.
- Overall survival is 92%.
The researchers concluded that Zevalin appears promising when used as part of a treatment regimen including high-dose chemotherapy prior to an autologous stem cell transplant. In order to fully understand and assess the clinical effectiveness of Zevalin, future clinical trials must directly compare regimens with Zevalin to full-body radiation in patients with NHL. Patients with recurrent NHL may wish to speak with their physician regarding their individual risks and benefits of treatment with Zevalin.
Reference: Nademanee A, Forman S, Molina A, et al. A phase ½ trial of high-dose yttrium-90-ibritumomab tiuxetan in combination with high-dose etoposide and cyclophosphamide followed by autologous stem cell transplant in patients with poor-risk or relapsed non-Hodgkin lymphoma. Blood. 2005;106:2896-2902
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