Radioimmunotherapy of Lymphoma: Bexxar and Zevalin

https://doi.org/10.1053/j.semnuclmed.2009.11.002Get rights and content

Radioimmunotherapy is a form of targeted radionuclide therapy that uses a monoclonal antibody to deliver localized radiation. It is most appropriate for treatment of multiple tumor sites that cannot be readily excised surgically or irradiated using external beam radiation or brachytherapy. At present, 2 products, Bexxar (131I-tositumomab and unlabeled tositumomab, GlaxoSmithKline, Triangle Park, NC) and Zevalin (90Y-ibritumomab tiuxetan and unlabeled rituximab, Spectrum Pharmaceuticals, Irvine, CA and Cell Therapeutics, Seattle, WA) are approved for treatment of non-Hodgkin's lymphoma in certain clinical situations in the United States and Canada. Zevalin is available also in Europe, and there are plans to make both agents more widely available. The therapeutic dose to be used depends upon a number of patient-specific variables. Both regimen achieve a complete response or partial response in approximately 3 of 4 patients, with a duration of remission lasting many years in some cases. This article reviews the basis for dose selection, the nuclear medicine procedures involved, the results obtained to date, and issues related to patient and staff safety.

Section snippets

B Cells and B-Cell Lymphoma

Non-Hodgkin's lymphomas are also broadly classified as either B-cell lymphomas or T-cell lymphomas, based on their lineage. B cells arise from reticuloendothelial elements in the prenatal liver and spleen, whereas T cells arise from the thymus. Because B cells evolve from the stem cell to mature lymphocytes and plasma cells, they express a variety of specific antigens that are characteristic of specific cell types. The expression of these epitopes varies as the cell matures and takes on

Radioimmunotherapy of B-Cell Lymphoma

This review deals with the basic issues involved in the development, the practical nuclear medicine aspects, and the clinical efficacy of 2 radiolabeled immunotherapeutic products, Bexxar and Zevalin, for the treatment of low-grade follicular B-cell lymphomas that are refractory or relapsed after treatment with the current best practice. These products are the first radiolabeled antibody regimen approved in the United States for the treatment of tumors. When specific issues are addressed, they

B-Cell Antigens

CD20 is one of many epitopes expressed on the mature B cell. Because it is so frequently expressed, it was selected early as a target for the development of monoclonal antibody therapy. Epitopes are protein components of cells that usually have a defined function and a distinct molecular configuration. For example, CD20 functions as a transmembrane calcium channel and is frequently expressed on both B cells and B-cell tumors. As stated earlier, CD20 appears as the B cell is maturing within the

Generic Issues: Bexxar and Zevalin

Currently, 2 radiolabeled antibodies are available for treatment of follicular low-grade non-Hodgkin's lymphoma, Bexxar and Zevalin. Bexxar contains 131I-labeled tositumomab, and Zevalin contains 90Y-labeled ibrutumomab. In both cases, the radiolabeled component is a murine anti-CD20 monoclonal antibody and in both cases, an unlabeled antibody is infused before the radiolabeled component is infused. The immunoreactivity of the 2 anti-CD20 murine monoclonal antibodies is not identical, but it is

Clinical Efficacy: RIT of Lymphoma

There are an abundance of clinical studies that demonstrate the efficacy of RIT of follicular low-grade non-Hodgkin's lymphoma. The initial and, at the time of this writing, current approval of both Bexxar and Zevalin was based on results in patients who were either refractory to, or relapsed after, rituximab therapy. Since that time, the use of rituximab has broadened considerably, and it is now used in many ways: as maintenance therapy after remission postchemotherapy, as an initial solo

Conclusions

Bexxar and Zevalin are approved by regulatory agencies, government, and private health insurance companies in the United States and Canada for the treatment of patients with follicular, low-grade non-Hodgkin's lymphoma. They produce significant improvement, sometimes with no evidence of disease (CR) for many months to several years. Other patients, with PRs, also remain symptom-free for long periods. The regimen were initially approved in patients who had relapsed or were refractory to previous

Acknowledgments

The author expresses gratitude and appreciation to colleagues present and past: Morton Coleman, MD, John Leonard, MD, Shankar Vallabhajosula, PhD, Vasilios Avlonitis, RPh, Zubaida Rahman, RPh, and Lale Kostakoglu, MD for their support during the period in which we worked together to understand and improve the principles and practice of radioimmunotherapy and to make this therapy available to patients with non-Hodgkin's lymphoma.

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