Journal
BLOOD
Volume 113, Issue 7, Pages 1412-1421Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2008-08-175653
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Funding
- National Institute for Health Research [NF-SI-0507-10049] Funding Source: researchfish
- Cancer Research UK [C328/A2738, C431/A3313] Funding Source: Medline
- Department of Health Funding Source: Medline
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The effect of induction therapy with multiple doses of rituximab on the subsequent efficacy and toxicity of anti-CD20 radioimmunotherapy is unknown. We evaluated a novel protocol using 4 weekly infusions of 375 mg/m(2) rituximab followed by 2 fractions of I-131-rituximab, preceded by a 100-mg/m(2) predose of rituximab, in relapsed indolent B-cell lymphoma. Induction therapy with rituximab significantly increased the effective half-life of I-131-rituximab (P = .003) and high serum levels of rituximab after induction therapy correlated with increased effective half-life of the radioimmunoconjugate (P = .009). Patients with large tumor burdens experienced significant increases in the effective half-life of I-131-rituximab between delivery of the first and second fractions (P = .007). Induction therapy with multiple doses of rituximab did not appear to compromise the clinical efficacy or increase toxicity of subsequent I-131-rituximab radioimmunotherapy. The overall response rate was 94%, with complete response rate 50%. The median time to progression was 20 months, significantly longer than for the last qualifying chemotherapy (P = .001). Fractionation of I-131-rituximab allowed cumulative whole-body doses of more than 120 cGy, approximately 60% greater than those previously achieved with a single administration of a murine radioimmunconjugate, to be delivered without significant hematologic toxicity. (Blood. 2009; 113: 1412-1421)
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