Journal article
A polymorphism in the complement component C1qA correlates with prolonged response following rituximab therapy of follicular lymphoma
Clinical cancer research, Vol.14(20), pp.6697-6703
10/15/2008
DOI: 10.1158/1078-0432.CCR-08-0745
PMCID: PMC2907116
PMID: 18927313
Abstract
Complement may play a role in the clinical response to rituximab and other monoclonal antibody-based therapies of cancer. The purpose of this study was to explore the relationship between the C1qA([276]) polymorphism and the clinical response to rituximab in patients with follicular lymphoma. Genotyping for C1qA([276A/G]) was done in 133 subjects with follicular lymphoma treated with single-agent rituximab, and correlation with clinical response was done using Cox regression analysis. Prolonged remission was observed among subjects that responded clinically to rituximab therapy and were carriers of the A allele compared with homozygous G subjects. Homozygous G subjects had a time to progression of 282 days, whereas A-allele carriers had a time to progression of 708 days [hazard ratio, (HR), 2.5; 95% confidence interval (95% CI), 2.0-3.1; P = 0.02]. Among subjects who achieved complete remission, homozygous G subjects had a time to progression of 250 days, whereas A-allele carriers had a time to progression of 1,118 days (HR, 4.5; 95% CI, 4.1-4.8, P = 0.04). The difference persisted after controlling for CD32 and CD16 polymorphisms. In patients who responded to rituximab used as first-line agent, a linear trend was observed among the C1qA([276]) genotypes, with homozygous A subjects achieving complete response at a higher rate compared with heterozygous or homozygous G subjects. Our findings indicate that polymorphisms in the C1qA gene may affect the clinical response and duration of response to rituximab therapy of follicular lymphoma. These results could have direct implications on designing antibodies with improved efficiency and enhance our understanding of the role of complement in monoclonal antibody therapy.
Details
- Title: Subtitle
- A polymorphism in the complement component C1qA correlates with prolonged response following rituximab therapy of follicular lymphoma
- Creators
- Emilian Racila - Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa 52242, USA. emil-racila@uiowa.eduBrian K LinkWen-Kai WengThomas E WitzigStephen AnsellMatthew J MaurerJian HuangChristopher DahleAhmad HalwaniRonald LevyGeorge J Weiner
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.14(20), pp.6697-6703
- Publisher
- United States
- DOI
- 10.1158/1078-0432.CCR-08-0745
- PMID
- 18927313
- PMCID
- PMC2907116
- ISSN
- 1078-0432
- eISSN
- 1557-3265
- Grant note
- U10 CA035113 / NCI NIH HHS CA35267 / NCI NIH HHS CA-35195 / NCI NIH HHS CS-35431 / PHS HHS K08 CA111827-02 / NCI NIH HHS P50 CA097274 / NCI NIH HHS R21 CA112904 / NCI NIH HHS CA-37404 / NCI NIH HHS CA-35415 / NCI NIH HHS CA-112904 / NCI NIH HHS U10 CA035448 / NCI NIH HHS CA-35101 / NCI NIH HHS K08 CA111827-03 / NCI NIH HHS CA-25224 / NCI NIH HHS P50-CA97274 / NCI NIH HHS CA-35448 / NCI NIH HHS CA-63826 / NCI NIH HHS U10 CA063848 / NCI NIH HHS U10 CA025224 / NCI NIH HHS CA-63848 / NCI NIH HHS U10 CA035415 / NCI NIH HHS CA-35090 / NCI NIH HHS CA-35113 / NCI NIH HHS U10 CA037404 / NCI NIH HHS CA-97274 / NCI NIH HHS CA-15083 / NCI NIH HHS
- Language
- English
- Date published
- 10/15/2008
- Academic Unit
- Statistics and Actuarial Science; Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Internal Medicine
- Record Identifier
- 9983985849302771
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