title: Phase 1/2 study of fractionated (131)I-rituximab in low-grade B-cell lymphoma: the effect of prior rituximab dosing and tumor burden on subsequent radioimmunotherapy.
abstract: 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 (131)I-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 (131)I-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 (131)I-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 (131)I-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 (131)I-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.
authors.affiliation: School of Cancer and Imaging Sciences, University of Manchester, Manchester, UK. tmi@manchester.ac.uk
authors.forename: Tim M
authors.initials: TM
authors.lastname: Illidge
authors.forename: Mike
authors.initials: M
authors.lastname: Bayne
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Brown
authors.forename: Samantha
authors.initials: S
authors.lastname: Chilton
authors.forename: Mark S
authors.initials: MS
authors.lastname: Cragg
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Glennie
authors.forename: Yong
authors.initials: Y
authors.lastname: Du
authors.forename: Valerie
authors.initials: V
authors.lastname: Lewington
authors.forename: James
authors.initials: J
authors.lastname: Smart
authors.forename: James
authors.initials: J
authors.lastname: Thom
authors.forename: Maureen
authors.initials: M
authors.lastname: Zivanovic
authors.forename: Peter W M
authors.initials: PW
authors.lastname: Johnson
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D058846:Antibodies, Monoclonal, Murine-Derived; D018572:Disease-Free Survival; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006454:Hemoglobins; D006801:Humans; D007457:Iodine Radioisotopes / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008198:Lymph Nodes / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology; D010976:Platelet Count; D016499:Radioimmunotherapy / Q000379:methods*; D000069283:Rituximab; D013154:Spleen / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D006454:Hemoglobins; D007457:Iodine Radioisotopes; D000069283:Rituximab; C507388:131I-rituximab