FCGR3A/2A polymorphisms and diffuse large B-cell lymphoma outcome treated with immunochemotherapy: a meta-analysis on 1134 patients from two prospective cohorts.
Details
Serval ID
serval:BIB_3EB5B0458CB1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
FCGR3A/2A polymorphisms and diffuse large B-cell lymphoma outcome treated with immunochemotherapy: a meta-analysis on 1134 patients from two prospective cohorts.
Journal
Hematological oncology
ISSN
1099-1069 (Electronic)
ISSN-L
0278-0232
Publication state
Published
Issued date
12/2017
Peer-reviewed
Oui
Volume
35
Number
4
Pages
447-455
Language
english
Notes
Publication types: Journal Article ; Meta-Analysis
Publication Status: ppublish
Publication Status: ppublish
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). Copyright © 2016 John Wiley & Sons, Ltd.
Keywords
Cohort Studies, Female, Genotype, Humans, Immunotherapy/methods, Lymphoma, Large B-Cell, Diffuse/drug therapy, Lymphoma, Large B-Cell, Diffuse/genetics, Lymphoma, Large B-Cell, Diffuse/pathology, Male, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Prognosis, Prospective Studies, Receptors, IgG/genetics, DLBCL, FCGR2A, FCGR3A, immunochemotherapy, polymorphisms, prognostic
Pubmed
Web of science
Create date
18/06/2016 18:36
Last modification date
20/08/2019 14:35