Radioimmunotherapy of B-cell lymphoma with radiolabelled anti-CD20 monoclonal antibodies.
CD20 has proven to be an excellent target for the treatment of B-cell lymphoma, first for the chimeric monoclonal antibody rituximab (Rituxan), and more recently for the radiolabelled antibodies Y-90 ibritumomab tiuxetan (Zevalin) and I-131 tositumomab (Bexxar). Radiation therapy effects are due to beta emissions with path lengths of 1-5 mm; gamma radiation emitted by I-131 is the only radiation safety issue for either product. Dose-limiting toxicity for both radiolabelled antibodies is reversible bone marrow suppression. They produce response rates of 70%-90% in low-grade and follicular lymphoma and 40%-50% in transformed low-grade or intermediate-grade lymphomas. Both products produce higher response rates than related unlabelled antibodies, and both are highly active in patients who are relatively resistant to rituximab-based therapy. Median duration of response to a single course of treatment is about 1 year with complete remission rates that last 2 years or longer in about 25% of patients. Clinical trials suggest that anti- CD20 radioimmunotherapy is superior to total body irradiation in patients undergoing stem cell supported therapy for B-cell lymphoma, and that it is a safe and efficacious modality when used as consolidation therapy following chemotherapy. Among cytotoxic treatment options, current evidence suggests that one course of anti-CD20 radioimmunotherapy is as efficacious as six to eight cycles of combination chemotherapy. A major question that persists is how effective these agents are in the setting of rituximab- refractory lymphoma. These products have been underutilised because of the complexity of treatment coordination and concerns regarding reimbursement.
Medical and Scientific Director, Hoag Cancer Center, Newport Beach, CA 92658, USA, rdillman@hoaghospital.org
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Dillman
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000276:immunology*; D002986:Clinical Trials as Topic; D006801:Humans; D016393:Lymphoma, B-Cell / Q000532:radiotherapy*; D016499:Radioimmunotherapy
D000911:Antibodies, Monoclonal; D018951:Antigens, CD20