FcγRIIa-H131R variant is associated with inferior response in diffuse large B cell lymphoma: A meta-analysis of genetic risk

Abstract

Purpose: Low-affinity variants FcγRIIIa-V158F and FcγRI-Ia-H131R may alter response to rituximab-based chemotherapy in diffuse large B-cell lymphoma (DLBCL) but available clinical evidence is inconclusive. Our purpose was to explore their association in terms of treatment response. Methods: We performed a meta-analysis of published literature to associate these variants with complete remission after upfront immunochemotherapy in DLBCL, and summarized the genetic risk using the model-free approach of generalized odds ratio (ORG). PubMed and EMBASE search (up to July 2014) yieldedfive pertinent studies. Results: FcγRIIa-H131R was associated with an inferior response to treatment (0Ra 0.67; 95%CI 0.46-0.97) and an additive mode of inheritance, with the genetic risk of heterozygotes assigned in the middle between high affinity (U/H.) and lower affinity (R/R) genotypes. This effect was unrelated to risk stratification, as no association was documented for FcγRIIa-H131R variant with the international prognostic index (IPI) (0Ra 1.02; 95%CI 0.79-1.31 for IPI 3-5 over 0-2). FcγRIIIa-V158F had no impact on treatment response but linkage disequilibrium and defective antibody-dependent cell-mediated cytotoxicity may have affected the outcome. Conclusion: FcγRIIa-H131R but not FcγRIIIa-V158F may modify treatment response in DLBCL.