FCGR3A/2A polymorphisms and diffuse large B-cell lymphoma outcome treated with immunochemotherapy: a meta-analysis on 1134 patients from two prospective cohorts.
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.
Department of Hematology, Centre Hospitalier Lyon Sud, Pierre-Bénite, France.|Centre de Recherche en Cancérologie de Lyon - INSERM U 1052/CNRS UMR 5286/Centre Léon Bérard, Lyon, France.|Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
Hervé
H
Ghesquières
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
Beth R
BR
Larrabee
Lymphoid Malignancies Unit, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP) and University Paris Est, Créteil, France.
Corinne
C
Haioun
Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA.
Brian K
BK
Link
Centre de Recherche en Cancérologie de Lyon - INSERM U 1052/CNRS UMR 5286/Centre Léon Bérard, Lyon, France.
Aurélie
A
Verney
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
Susan L
SL
Slager
Department of Oncology, University Hospital, Lausanne, Switzerland.
Nicolas
N
Ketterer
Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
Stephen M
SM
Ansell
Department of Hematology, Necker Hospital, Paris, France.
Richard
R
Delarue
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
Matthew J
MJ
Maurer
Onco-Hematology, Polyclinique Bordeaux-Nord, Bordeaux, France.
Olivier
O
Fitoussi
Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
Thomas M
TM
Habermann
Medical Oncology, Centre Antoine Lacassagne, Nice, France.
Fréderic
F
Peyrade
Departments of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Ahmet
A
Dogan
Department of Pathology, Necker Hospital, Paris, France.
Thierry J
TJ
Molina
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
Anne J
AJ
Novak
Department of Hematology, Centre Henri Becquerel, Rouen, France.
Hervé
H
Tilly
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
James R
JR
Cerhan
Department of Hematology, Centre Hospitalier Lyon Sud, Pierre-Bénite, France.|Centre de Recherche en Cancérologie de Lyon - INSERM U 1052/CNRS UMR 5286/Centre Léon Bérard, Lyon, France.
Gilles
G
Salles
D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011446:Prospective Studies; D017452:Receptors, IgG / Q000235:genetics*
C496124:FCGR3A protein, human; D017452:Receptors, IgG
DLBCL; FCGR2A; FCGR3A; immunochemotherapy; polymorphisms; prognostic