A polymorphism in the complement component C1qA correlates with prolonged response following rituximab therapy of follicular lymphoma

Emilian Racila, Brian K. Link, Wen Kai Weng, Thomas Elmer Witzig, Stephen Maxted Ansell, Matthew J. Maurer, Jian Huang, Christopher Dahle, Ahmad Halwani, Ronald Levy, George J. Werner

Research output: Contribution to journalArticle

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Abstract

Purpose: 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. Experimental Design: 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. Results: Prolonged remission was observed among subjects that responded clinically to rituximab therapy and were carriers of the Aallele 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 Asubjects achieving complete response at a higher rate compared with heterozygous or homozygous G subjects. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)6697-6703
Number of pages7
JournalClinical Cancer Research
Volume14
Issue number20
DOIs
StatePublished - Oct 15 2008

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Follicular Lymphoma
Therapeutics
Alleles
Monoclonal Antibodies
Confidence Intervals
Rituximab
Research Design
Genotype
Regression Analysis
Antibodies
Genes
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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A polymorphism in the complement component C1qA correlates with prolonged response following rituximab therapy of follicular lymphoma. / Racila, Emilian; Link, Brian K.; Weng, Wen Kai; Witzig, Thomas Elmer; Ansell, Stephen Maxted; Maurer, Matthew J.; Huang, Jian; Dahle, Christopher; Halwani, Ahmad; Levy, Ronald; Werner, George J.

In: Clinical Cancer Research, Vol. 14, No. 20, 15.10.2008, p. 6697-6703.

Research output: Contribution to journalArticle

Racila, Emilian ; Link, Brian K. ; Weng, Wen Kai ; Witzig, Thomas Elmer ; Ansell, Stephen Maxted ; Maurer, Matthew J. ; Huang, Jian ; Dahle, Christopher ; Halwani, Ahmad ; Levy, Ronald ; Werner, George J. / A polymorphism in the complement component C1qA correlates with prolonged response following rituximab therapy of follicular lymphoma. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 20. pp. 6697-6703.
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abstract = "Purpose: 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. Experimental Design: 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. Results: Prolonged remission was observed among subjects that responded clinically to rituximab therapy and were carriers of the Aallele 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 Asubjects achieving complete response at a higher rate compared with heterozygous or homozygous G subjects. Conclusions: 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.",
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T1 - A polymorphism in the complement component C1qA correlates with prolonged response following rituximab therapy of follicular lymphoma

AU - Racila, Emilian

AU - Link, Brian K.

AU - Weng, Wen Kai

AU - Witzig, Thomas Elmer

AU - Ansell, Stephen Maxted

AU - Maurer, Matthew J.

AU - Huang, Jian

AU - Dahle, Christopher

AU - Halwani, Ahmad

AU - Levy, Ronald

AU - Werner, George J.

PY - 2008/10/15

Y1 - 2008/10/15

N2 - Purpose: 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. Experimental Design: 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. Results: Prolonged remission was observed among subjects that responded clinically to rituximab therapy and were carriers of the Aallele 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 Asubjects achieving complete response at a higher rate compared with heterozygous or homozygous G subjects. Conclusions: 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.

AB - Purpose: 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. Experimental Design: 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. Results: Prolonged remission was observed among subjects that responded clinically to rituximab therapy and were carriers of the Aallele 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 Asubjects achieving complete response at a higher rate compared with heterozygous or homozygous G subjects. Conclusions: 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.

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