FCyIIIa Gene Polymorphisms as Response Predictor in Patients with Non-Hodgkin Lymphoma after Treatment with Anti-CD 20 Monoclonal Antibody (Rituximab).

Abstract

Background: The main mechanism of action of rituximab is through antibody-dependent cellular cytotoxicity via Fc receptors for immunoglobulin G. Recently a polymorphism of Fc was reported, which consists in the substitution of phenylalanine for valine in position 158. Patients with homozygous 158 valine/valine (V/V) alleles of Fc showed a higher response rate to rituximab treatment in contrast to patients with phenylalanine/valine (F/V) or homozygous phenilalanine (F/F). It would have clinical value to know which patients could have a greater benefit from the treatment with rituximab. Aims: 1-to determine the Fc genotype in patients with Non-Hodgkin lymphoma (NHL) in our population. 2- to analyze the response rate to rituximab of these patients according to the Fc polymorphism. Methods: DNA was isolated from peripheral blood. Genotyping of FCyIIIa polymorphism was performed using a polymerase chain reaction and were confirmed by direct sequencing of the region of interest. To analyse the results the patients were divided into two groups: with valine expression: V/V or V/F, and without valine expression F/F. The response was evaluated after 3 months of treatment and at the end of it. Chi-square and Fisher’s exact tests were used for statistical analysis. Results: 34 patients with NHL: 19 follicular lymphoma, 12 diffuse large B-cell lymphoma, 3 mantle lymphoma. The FcyIIIa polymorphism expression was 11.8% V/V, 52.9% V/F and 35.3% F/F. The complete response (CR) after 3 months of treatment was 50% and 41.7% for V/V-V/F and F/F respectively (not statistically significant (ns)). After end of treatment CR was 86.7% in V/V-V/F and 72.7% in F/F(ns). In patients with follicular lymphoma the CR after end of treatment was 87.5% in V/V-V/F and 79% in F/F (ns). In patients with diffuse large B-cell lymphoma the CR was reached in all patients regardless of polymorphism. Conclusions: FcyIIIa gene polymorphism did not help in predicting response after treatment with rituximab in our group of patients with NHL. A large number of patients would be necessary to draw conclusions, especially in the group with follicular lymphoma.