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

Authors: Ghesquieres, H  Larrabee, BR  Haioun, C  Link, BK  Verney, A  Slager, SL  Ketterer, N  Ansell, SM  Delarue, R  Maurer, MJ  Fitoussi, O  Habermann, TM  Peyrade, F  Dogan, A  Molina, TJ  Novak, AJ  Tilly, H  Cerhan, JR  Salles, G 
Citation: Ghesquieres H, etal., Hematol Oncol. 2016 Jun 10. doi: 10.1002/hon.2305.
Pubmed: (View Article at PubMed) PMID:27282998
DOI: Full-text: DOI:10.1002/hon.2305

Single nucleotide polymorphisms (SNPs) in FCgamma-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 FCgammaRIIA RR had an unexpectedly better outcome than FCgammaRIIA H carriers. Whether rituximab efficacy is improved in FCgammaRIIA RR patients due a clearance reduction or other functions of FCgammaRIIA in DLBCL should be investigated (clinicaltrials.gov identifiers: NCT00135499, NTC00135499 NCT00140595, NCT00144807, NCT00144755, NCT01087424, and NCT00301821). Copyright (c) 2016 John Wiley & Sons, Ltd.

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RGD Object Information
RGD ID: 11344967
Created: 2016-07-11
Species: All species
Last Modified: 2016-07-11
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.