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

Autor: Ghesquières H; 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., Larrabee BR; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA., Haioun C; Lymphoid Malignancies Unit, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP) and University Paris Est, Créteil, France., Link BK; Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA., Verney A; Centre de Recherche en Cancérologie de Lyon - INSERM U 1052/CNRS UMR 5286/Centre Léon Bérard, Lyon, France., Slager SL; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA., Ketterer N; Department of Oncology, University Hospital, Lausanne, Switzerland., Ansell SM; Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA., Delarue R; Department of Hematology, Necker Hospital, Paris, France., Maurer MJ; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA., Fitoussi O; Onco-Hematology, Polyclinique Bordeaux-Nord, Bordeaux, France., Habermann TM; Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA., Peyrade F; Medical Oncology, Centre Antoine Lacassagne, Nice, France., Dogan A; Departments of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Molina TJ; Department of Pathology, Necker Hospital, Paris, France., Novak AJ; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA., Tilly H; Department of Hematology, Centre Henri Becquerel, Rouen, France., Cerhan JR; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA., Salles G; 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.
Jazyk: angličtina
Zdroj: Hematological oncology [Hematol Oncol] 2017 Dec; Vol. 35 (4), pp. 447-455. Date of Electronic Publication: 2016 Jun 10.
DOI: 10.1002/hon.2305
Abstrakt: 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.
(Copyright © 2016 John Wiley & Sons, Ltd.)
Databáze: MEDLINE
Externí odkaz: