FCGR3A/2A polymorphisms and diffuse large B-cell lymphoma outcome treated with immunochemotherapy: A meta-analysis on 1134 patients from two prospective cohorts

Hervé Ghesquières, Beth R. Larrabee, Corinne Haioun, Brian K. Link, Aurélie Verney, Susan L Slager, Nicolas Ketterer, Stephen Maxted Ansell, Richard Delarue, Matthew J. Maurer, Olivier Fitoussi, Thomas Matthew Habermann, Fréderic Peyrade, Ahmet Dogan, Thierry J. Molina, Anne J Novak, Hervé Tilly, James R Cerhan, Gilles Salles

Research output: Contribution to journalArticle

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Abstract

Single nucleotide polymorphisms (SNPs) in FCγ-receptor genes FCGR3A (rs396991) and FCGR2A (rs1801274) influence the affinity of the Fc portion of anti-CD20 immunoglobulin G1 monoclonal antibody. Their roles in diffuse large B-cell lymphoma (DLBCL) treated with rituximab in combination with anthracycline-based chemotherapy remain controversial. To address this question, we genotyped FCGR2A and FCGR3A SNPs in two prospective DLBCL cohorts from Lymphoma Study Association trials (N=554) and Iowa/Mayo Specialized Program Of Research Excellence (N=580). Correlations with treatment response and hematological toxicity were assessed in Lymphoma Study Association. Correlation with event-free survival (EFS) and overall survival (OS) was performed in both cohorts, followed by a meta-analysis to increase power. Our study shows the absence of correlation between these SNPs and treatment response. Grades 3 and 4 febrile neutropenia during treatment was more frequently observed in FCGR3A VV (39%) than VF (29%) and FF (32%) carriers (p=0.04). Our analysis for EFS and OS shows that FCGR3A was not associated with outcome. In a meta-analysis using an ordinal model, FCGR2A (per R allele) was associated with a better EFS (hazard ratio=0.87; 95%CI, 0.76-0.99; p=0.04) and OS (hazard ratio=0.86; 95%CI, 0.73-1.00; p=0.05) which was not altered after adjustment for the International Prognostic Index. Overall, our data demonstrate that patients with DLBCL with the low-affinity FCγRIIA RR had an unexpectedly better outcome than FCγRIIA H carriers. Whether rituximab efficacy is improved in FCγRIIA RR patients due a clearance reduction or other functions of FCγRIIA in DLBCL should be investigated (clinicaltrials.gov identifiers: NCT00135499, NTC00135499 NCT00140595, NCT00144807, NCT00144755, NCT01087424, and NCT00301821).

Original languageEnglish (US)
JournalHematological Oncology
DOIs
StateAccepted/In press - 2016

Fingerprint

Lymphoma, Large B-Cell, Diffuse
Meta-Analysis
Disease-Free Survival
Single Nucleotide Polymorphism
Survival
Lymphoma
Febrile Neutropenia
Anthracyclines
Immunoglobulins
Cohort Studies
Therapeutics
Alleles
Monoclonal Antibodies
Drug Therapy
Research
Genes
Rituximab

Keywords

  • DLBCL
  • FCGR2A
  • FCGR3A
  • Immunochemotherapy
  • Polymorphisms
  • Prognostic

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

FCGR3A/2A polymorphisms and diffuse large B-cell lymphoma outcome treated with immunochemotherapy : A meta-analysis on 1134 patients from two prospective cohorts. / Ghesquières, Hervé; Larrabee, Beth R.; Haioun, Corinne; Link, Brian K.; Verney, Aurélie; Slager, Susan L; Ketterer, Nicolas; Ansell, Stephen Maxted; Delarue, Richard; Maurer, Matthew J.; Fitoussi, Olivier; Habermann, Thomas Matthew; Peyrade, Fréderic; Dogan, Ahmet; Molina, Thierry J.; Novak, Anne J; Tilly, Hervé; Cerhan, James R; Salles, Gilles.

In: Hematological Oncology, 2016.

Research output: Contribution to journalArticle

Ghesquières, Hervé ; Larrabee, Beth R. ; Haioun, Corinne ; Link, Brian K. ; Verney, Aurélie ; Slager, Susan L ; Ketterer, Nicolas ; Ansell, Stephen Maxted ; Delarue, Richard ; Maurer, Matthew J. ; Fitoussi, Olivier ; Habermann, Thomas Matthew ; Peyrade, Fréderic ; Dogan, Ahmet ; Molina, Thierry J. ; Novak, Anne J ; Tilly, Hervé ; Cerhan, James R ; Salles, Gilles. / FCGR3A/2A polymorphisms and diffuse large B-cell lymphoma outcome treated with immunochemotherapy : A meta-analysis on 1134 patients from two prospective cohorts. In: Hematological Oncology. 2016.
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abstract = "Single nucleotide polymorphisms (SNPs) in FCγ-receptor genes FCGR3A (rs396991) and FCGR2A (rs1801274) influence the affinity of the Fc portion of anti-CD20 immunoglobulin G1 monoclonal antibody. Their roles in diffuse large B-cell lymphoma (DLBCL) treated with rituximab in combination with anthracycline-based chemotherapy remain controversial. To address this question, we genotyped FCGR2A and FCGR3A SNPs in two prospective DLBCL cohorts from Lymphoma Study Association trials (N=554) and Iowa/Mayo Specialized Program Of Research Excellence (N=580). Correlations with treatment response and hematological toxicity were assessed in Lymphoma Study Association. Correlation with event-free survival (EFS) and overall survival (OS) was performed in both cohorts, followed by a meta-analysis to increase power. Our study shows the absence of correlation between these SNPs and treatment response. Grades 3 and 4 febrile neutropenia during treatment was more frequently observed in FCGR3A VV (39{\%}) than VF (29{\%}) and FF (32{\%}) carriers (p=0.04). Our analysis for EFS and OS shows that FCGR3A was not associated with outcome. In a meta-analysis using an ordinal model, FCGR2A (per R allele) was associated with a better EFS (hazard ratio=0.87; 95{\%}CI, 0.76-0.99; p=0.04) and OS (hazard ratio=0.86; 95{\%}CI, 0.73-1.00; p=0.05) which was not altered after adjustment for the International Prognostic Index. Overall, our data demonstrate that patients with DLBCL with the low-affinity FCγRIIA RR had an unexpectedly better outcome than FCγRIIA H carriers. Whether rituximab efficacy is improved in FCγRIIA RR patients due a clearance reduction or other functions of FCγRIIA in DLBCL should be investigated (clinicaltrials.gov identifiers: NCT00135499, NTC00135499 NCT00140595, NCT00144807, NCT00144755, NCT01087424, and NCT00301821).",
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T1 - FCGR3A/2A polymorphisms and diffuse large B-cell lymphoma outcome treated with immunochemotherapy

T2 - A meta-analysis on 1134 patients from two prospective cohorts

AU - Ghesquières, Hervé

AU - Larrabee, Beth R.

AU - Haioun, Corinne

AU - Link, Brian K.

AU - Verney, Aurélie

AU - Slager, Susan L

AU - Ketterer, Nicolas

AU - Ansell, Stephen Maxted

AU - Delarue, Richard

AU - Maurer, Matthew J.

AU - Fitoussi, Olivier

AU - Habermann, Thomas Matthew

AU - Peyrade, Fréderic

AU - Dogan, Ahmet

AU - Molina, Thierry J.

AU - Novak, Anne J

AU - Tilly, Hervé

AU - Cerhan, James R

AU - Salles, Gilles

PY - 2016

Y1 - 2016

N2 - Single nucleotide polymorphisms (SNPs) in FCγ-receptor genes FCGR3A (rs396991) and FCGR2A (rs1801274) influence the affinity of the Fc portion of anti-CD20 immunoglobulin G1 monoclonal antibody. Their roles in diffuse large B-cell lymphoma (DLBCL) treated with rituximab in combination with anthracycline-based chemotherapy remain controversial. To address this question, we genotyped FCGR2A and FCGR3A SNPs in two prospective DLBCL cohorts from Lymphoma Study Association trials (N=554) and Iowa/Mayo Specialized Program Of Research Excellence (N=580). Correlations with treatment response and hematological toxicity were assessed in Lymphoma Study Association. Correlation with event-free survival (EFS) and overall survival (OS) was performed in both cohorts, followed by a meta-analysis to increase power. Our study shows the absence of correlation between these SNPs and treatment response. Grades 3 and 4 febrile neutropenia during treatment was more frequently observed in FCGR3A VV (39%) than VF (29%) and FF (32%) carriers (p=0.04). Our analysis for EFS and OS shows that FCGR3A was not associated with outcome. In a meta-analysis using an ordinal model, FCGR2A (per R allele) was associated with a better EFS (hazard ratio=0.87; 95%CI, 0.76-0.99; p=0.04) and OS (hazard ratio=0.86; 95%CI, 0.73-1.00; p=0.05) which was not altered after adjustment for the International Prognostic Index. Overall, our data demonstrate that patients with DLBCL with the low-affinity FCγRIIA RR had an unexpectedly better outcome than FCγRIIA H carriers. Whether rituximab efficacy is improved in FCγRIIA RR patients due a clearance reduction or other functions of FCγRIIA in DLBCL should be investigated (clinicaltrials.gov identifiers: NCT00135499, NTC00135499 NCT00140595, NCT00144807, NCT00144755, NCT01087424, and NCT00301821).

AB - Single nucleotide polymorphisms (SNPs) in FCγ-receptor genes FCGR3A (rs396991) and FCGR2A (rs1801274) influence the affinity of the Fc portion of anti-CD20 immunoglobulin G1 monoclonal antibody. Their roles in diffuse large B-cell lymphoma (DLBCL) treated with rituximab in combination with anthracycline-based chemotherapy remain controversial. To address this question, we genotyped FCGR2A and FCGR3A SNPs in two prospective DLBCL cohorts from Lymphoma Study Association trials (N=554) and Iowa/Mayo Specialized Program Of Research Excellence (N=580). Correlations with treatment response and hematological toxicity were assessed in Lymphoma Study Association. Correlation with event-free survival (EFS) and overall survival (OS) was performed in both cohorts, followed by a meta-analysis to increase power. Our study shows the absence of correlation between these SNPs and treatment response. Grades 3 and 4 febrile neutropenia during treatment was more frequently observed in FCGR3A VV (39%) than VF (29%) and FF (32%) carriers (p=0.04). Our analysis for EFS and OS shows that FCGR3A was not associated with outcome. In a meta-analysis using an ordinal model, FCGR2A (per R allele) was associated with a better EFS (hazard ratio=0.87; 95%CI, 0.76-0.99; p=0.04) and OS (hazard ratio=0.86; 95%CI, 0.73-1.00; p=0.05) which was not altered after adjustment for the International Prognostic Index. Overall, our data demonstrate that patients with DLBCL with the low-affinity FCγRIIA RR had an unexpectedly better outcome than FCγRIIA H carriers. Whether rituximab efficacy is improved in FCγRIIA RR patients due a clearance reduction or other functions of FCγRIIA in DLBCL should be investigated (clinicaltrials.gov identifiers: NCT00135499, NTC00135499 NCT00140595, NCT00144807, NCT00144755, NCT01087424, and NCT00301821).

KW - DLBCL

KW - FCGR2A

KW - FCGR3A

KW - Immunochemotherapy

KW - Polymorphisms

KW - Prognostic

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