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.
dc.contributor.author | Illidge, Timothy M | |
dc.contributor.author | Bayne, Mike | |
dc.contributor.author | Brown, Nicholas S | |
dc.contributor.author | Chilton, Samantha | |
dc.contributor.author | Cragg, Mark S | |
dc.contributor.author | Glennie, Martin J | |
dc.contributor.author | Du, Yong | |
dc.contributor.author | Lewington, Valerie | |
dc.contributor.author | Smart, James | |
dc.contributor.author | Thom, James | |
dc.contributor.author | Zivanovic, Maureen | |
dc.contributor.author | Johnson, Peter W | |
dc.date.accessioned | 2010-03-15T16:39:37Z | |
dc.date.available | 2010-03-15T16:39:37Z | |
dc.date.issued | 2009-02-12 | |
dc.identifier.citation | 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. 2009, 113 (7):1412-21 Blood | en |
dc.identifier.issn | 1528-0020 | |
dc.identifier.pmid | 19074729 | |
dc.identifier.doi | 10.1182/blood-2008-08-175653 | |
dc.identifier.uri | http://hdl.handle.net/10541/94249 | |
dc.description.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. | |
dc.language.iso | en | en |
dc.subject | Haemoglobin | en |
dc.subject.mesh | Adult | |
dc.subject.mesh | Aged | |
dc.subject.mesh | Antibodies, Monoclonal | |
dc.subject.mesh | Disease-Free Survival | |
dc.subject.mesh | Dose-Response Relationship, Radiation | |
dc.subject.mesh | Female | |
dc.subject.mesh | Hemoglobins | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Iodine Radioisotopes | |
dc.subject.mesh | Lymph Nodes | |
dc.subject.mesh | Lymphoma, B-Cell | |
dc.subject.mesh | Male | |
dc.subject.mesh | Middle Aged | |
dc.subject.mesh | Neutrophils | |
dc.subject.mesh | Platelet Count | |
dc.subject.mesh | Radioimmunotherapy | |
dc.subject.mesh | Spleen | |
dc.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. | en |
dc.type | Article | en |
dc.contributor.department | School of Cancer and Imaging Sciences, University of Manchester, Manchester, UK. tmi@manchester.ac.uk | en |
dc.identifier.journal | Blood | en |
html.description.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. |