Journal article
FCGR3A/2A polymorphisms and diffuse large B-cell lymphoma outcome treated with immunochemotherapy: a meta-analysis on 1134 patients from two prospective cohorts
Hematological oncology, Vol.35(4), pp.447-455
12/2017
DOI: 10.1002/hon.2305
PMCID: PMC5716925
PMID: 27282998
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.
Details
- Title: Subtitle
- FCGR3A/2A polymorphisms and diffuse large B-cell lymphoma outcome treated with immunochemotherapy: a meta-analysis on 1134 patients from two prospective cohorts
- Creators
- Hervé Ghesquières - Centre Léon BérardBeth R Larrabee - Mayo ClinicCorinne Haioun - Assistance Publique – Hôpitaux de ParisBrian K Link - University of IowaAurélie Verney - Centre Léon BérardSusan L Slager - Mayo ClinicNicolas Ketterer - University Hospital of LausanneStephen M Ansell - Mayo ClinicRichard Delarue - Hôpital Necker-Enfants MaladesMatthew J Maurer - Mayo ClinicOlivier Fitoussi - Onco‐Hematology, Polyclinique Bordeaux‐Nord Bordeaux FranceThomas M Habermann - Mayo ClinicFréderic Peyrade - Centre Antoine LacassagneAhmet Dogan - Memorial Sloan Kettering Cancer CenterThierry J Molina - Hôpital Necker-Enfants MaladesAnne J Novak - Mayo ClinicHervé Tilly - Department of Hematology Centre Henri Becquerel Rouen FranceJames R Cerhan - Mayo ClinicGilles Salles - Centre Léon Bérard
- Resource Type
- Journal article
- Publication Details
- Hematological oncology, Vol.35(4), pp.447-455
- DOI
- 10.1002/hon.2305
- PMID
- 27282998
- PMCID
- PMC5716925
- ISSN
- 0278-0232
- eISSN
- 1099-1069
- Grant note
- R01 CA129539 / NCI NIH HHS P30 CA086862 / NCI NIH HHS P50 CA097274 / NCI NIH HHS
- Language
- English
- Date published
- 12/2017
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Internal Medicine
- Record Identifier
- 9984359762702771
Metrics
14 Record Views