Radioimmunotherapy of non-Hodgkin's lymphoma

Non-Hodgkin's lymphomas (NHL) are malignancies derived from lymphocytes with approximately 80% involving B-cell lymphocytes and 95% of B-cell lymphomas expressing the CD20 antigen on the tumor cell surface membrane. Although NHL is considered a curable disease, many patients especially those with indolent NHL relapse and eventually die. For patients with limited stage disease, conventional radiation therapy is utilized. For advanced stage disease combination chemotherapy and Rituximab, a chimeric anti-CD20 monoclonal antibody is the standard therapy. Radioimmunotherapy is a recent addition for treatment of NHL and utilizes a tumor cell targeting monoclonal antibody chemically linked to a therapeutic radionuclide delivering radiation to tumor cells while limiting toxicity to normal cells. The advantage of radioimmunotherapy is the ability to treat multiple tumor sites throughout the body following intravenous infusion. The most common radionuclides used for radioimmunotherapy have been 131Iodine (I-131) and more recently 90Yttrium (Y-90). Y-90 is bound to the monoclonal antibody using metal chelating groups while I-131 is directly linked to the antibody. Phase I, II and III therapy trials of I-131 or Y-90 labeled anti-CD20 monoclonal antibodies have shown radioimmunotherapy to be safe and highly effective in the treatment of B-cell NHL. Transient hematologic toxicity with nadirs occurring at 7 to 9 weeks and lasting approximately 1 to 2 weeks has been the only side-effects. The response rates from radioimmunotherapy have been higher than for the unlabeled antibody therapy (Y-90 anti-CD20 vs. Rituximab response rates = 80% vs. 56% ( p = 0.002) and complete response (CR) rates were 30% and 16% respectively (p=0.04). Radiolabeled anti-CD20 monoclonal antibodies are now being used alone or in combination with chemotherapy, external beam radiation or stem cell transplantation for treating patients with NHL. Radioimmunotherapy has become a value new treatment for patients with NHL taking advantage of the radiation sensitivity of lymphoma cells and the tumor specific targeting of monoclonal antibodies