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Phase 1/2 study of fractionated 131I-rituximab in low-grade B-cell lymphoma: the effect of prior rituximab dosing and tumor burden on subsequent radioimmunotherapy

Phase 1/2 study of fractionated 131I-rituximab in low-grade B-cell lymphoma: the effect of prior rituximab dosing and tumor burden on subsequent radioimmunotherapy
Phase 1/2 study of fractionated 131I-rituximab in low-grade B-cell lymphoma: the effect of prior rituximab dosing and tumor burden on subsequent radioimmunotherapy
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/m2 rituximab followed by 2 fractions of 131I-rituximab, preceded by a 100-mg/m2 predose of rituximab, in relapsed indolent B-cell lymphoma. Induction therapy with rituximab significantly increased the effective half-life of 131I-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 131I-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 131I-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 131I-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.
0006-4971
1412-1421
Illidge, Tim M.
2a7357b3-0340-42bc-9716-2dd278590747
Bayne, Mike
f20fcb02-8b09-44b1-ae71-ab8952f38cdc
Brown, Nicholas S.
3e33b340-2396-4660-97c3-6556a37ca82d
Chilton, Samantha
31f49fce-0253-4a01-a0ef-5df4a6880279
Cragg, Mark S.
ec97f80e-f3c8-49b7-a960-20dff648b78c
Glennie, Martin J.
7c33c8f5-20b9-45b0-8ced-1243576f2fa0
Du, Yong
5ae897d7-a3db-45d7-896a-187afa95ac43
Lewington, Valerie
eac05855-c5a8-41a3-ba7d-b144356777ab
Smart, James
602a8e42-2d0b-4306-86db-8b1395e86254
Thom, James
b7ec3ef3-95cc-4be4-8a72-bd01524aa4c1
Zivanovic, Maureen
c1b34abe-e6b5-4fa0-9c4b-48a8e79c3ccf
Johnson, Peter W.M.
3f6068ce-171e-4c2c-aca9-dc9b6a37413f
Illidge, Tim M.
2a7357b3-0340-42bc-9716-2dd278590747
Bayne, Mike
f20fcb02-8b09-44b1-ae71-ab8952f38cdc
Brown, Nicholas S.
3e33b340-2396-4660-97c3-6556a37ca82d
Chilton, Samantha
31f49fce-0253-4a01-a0ef-5df4a6880279
Cragg, Mark S.
ec97f80e-f3c8-49b7-a960-20dff648b78c
Glennie, Martin J.
7c33c8f5-20b9-45b0-8ced-1243576f2fa0
Du, Yong
5ae897d7-a3db-45d7-896a-187afa95ac43
Lewington, Valerie
eac05855-c5a8-41a3-ba7d-b144356777ab
Smart, James
602a8e42-2d0b-4306-86db-8b1395e86254
Thom, James
b7ec3ef3-95cc-4be4-8a72-bd01524aa4c1
Zivanovic, Maureen
c1b34abe-e6b5-4fa0-9c4b-48a8e79c3ccf
Johnson, Peter W.M.
3f6068ce-171e-4c2c-aca9-dc9b6a37413f

Illidge, Tim M., Bayne, Mike, Brown, Nicholas S., Chilton, Samantha, Cragg, Mark S., Glennie, Martin J., Du, Yong, Lewington, Valerie, Smart, James, Thom, James, Zivanovic, Maureen and Johnson, Peter W.M. (2008) Phase 1/2 study of fractionated 131I-rituximab in low-grade B-cell lymphoma: the effect of prior rituximab dosing and tumor burden on subsequent radioimmunotherapy. Blood, 113 (7), 1412-1421. (doi:10.1182/blood-2008-08-175653). (PMID:19074729)

Record type: Article

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/m2 rituximab followed by 2 fractions of 131I-rituximab, preceded by a 100-mg/m2 predose of rituximab, in relapsed indolent B-cell lymphoma. Induction therapy with rituximab significantly increased the effective half-life of 131I-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 131I-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 131I-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 131I-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.

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Published date: 12 December 2008
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 149075
URI: http://eprints.soton.ac.uk/id/eprint/149075
ISSN: 0006-4971
PURE UUID: 662f5853-48a1-4a15-b3f7-6ade789b2c6b
ORCID for Mark S. Cragg: ORCID iD orcid.org/0000-0003-2077-089X
ORCID for Peter W.M. Johnson: ORCID iD orcid.org/0000-0003-2306-4974

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Date deposited: 29 Apr 2010 15:02
Last modified: 14 Mar 2024 02:41

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Contributors

Author: Tim M. Illidge
Author: Mike Bayne
Author: Nicholas S. Brown
Author: Samantha Chilton
Author: Mark S. Cragg ORCID iD
Author: Martin J. Glennie
Author: Yong Du
Author: Valerie Lewington
Author: James Smart
Author: James Thom
Author: Maureen Zivanovic

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