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.
Dillman
R O
RO
Medical and Scientific Director, Hoag Cancer Center, Newport Beach, CA 92658, USA, rdillman@hoaghospital.org
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