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

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.

• Authors: Hervé Ghesquières, Beth R Larrabee, Corinne Haioun, Brian K Link, Aurélie Verney, Susan L Slager, Nicolas Ketterer, Stephen M Ansell, Richard Delarue, Matthew J Maurer, Olivier Fitoussi, Thomas M Habermann, Fréderic Peyrade, Ahmet Dogan, Thierry J Molina, Anne J Novak, Hervé Tilly, James R Cerhan, Gilles Salles
• Journal: Hematological oncology (Hematol Oncol) Vol. 35 Issue 4 Pg. 447-455 (Dec 2017) ISSN: 1099-1069 [Electronic] England
• PMID: 27282998 (Publication Type: Journal Article, Meta-Analysis)
• Copyright: Copyright © 2016 John Wiley & Sons, Ltd.

Chemical References

• FCGR3A protein, human
• Receptors, IgG

Topics

• Cohort Studies
• Female
• Genotype
• Humans
• Immunotherapy (methods)
• Lymphoma, Large B-Cell, Diffuse (drug therapy, genetics, pathology)
• Male
• Polymorphism, Genetic
• Polymorphism, Single Nucleotide
• Prognosis
• Prospective Studies
• Receptors, IgG (genetics)