FCγRIIa Polymorphism Is Not Associated with Overall Response in Diffuse Large B-Cell Lymphoma Treated with Rituximab.

Low-affinity receptor for the Fc region of immunoglobulin G (IgG) (FcγR) is constitutively expressed on resting human neutrophils. These receptor, termed FcγRIIa display biallelic polymorphism which have functional consequences with respect to binding and/or ingestion of targets opsonized by human IgG subclass antibodies. Rituximab is a chimeric monoclonal antibody directed against CD20, an antigen found in most B-cell malignancies. Multiple mechanisms have been proposed for the activity of Rituximab, including antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and a direct proapoptotic effect. F(ab')₂ Rituximab homodimers were shown to be effective in inducing apoptosis of B-cell lymphoma cell lines in vitro. Recently, it have been established that ADCC is important as predominant mechanism of lymphoma cell clearance and that Fcγ receptors (FcγRs) are critical for the in vivo actions of Rituximab in non-Hodgkin lymphoma (NHL). A genomic polymorphism at amino acid 131 of FcγRIIA has been described whereby the presence of Histidine (H) rather than Arginine is associated with responses to the CD20-directed immunoglobulin G1 (IgG1) Rituximab among patients with indolent lymphoma. FcγRIIA genotype have been associated with a better clinical and molecular response in follicular lymphoma patients treated as first line therapy with Rituximab alone and in patients with diffuse large B-cell lymphoma (DLBCL) treated with the concomitant administration of Rituximab and CHOP (R-CHOP).

Here we analyzed the role of specific polymorphism of activating FcγRIIA in 42 patients with DLBCL treated with R-CHOP concerning prediction complete response (CR) using a polymerase chain reaction-restriction fragment length polymorphism method.

The median age of the patients was 48 years (15 to 82). Out of the 42 patients 18 (42.8%) were stage III-IV and 17 (40.4%) had more than 2 factors of the International Prognostic Index. Thirty-seven (87.6%) had CR, 1 (2.3%) had partial remission (PR) and 4 (10.1%) had refractory disease (RD). Four ( 10.8%) of the patients that acquired CR relapsed. Deaths occurred in 3 (7.1%) patients with follow up of 2 years. Eight (19%) patients showed polymorphism HH, 21 (50%) HR and 13 (31%) RR. The univariate analysis did not show correlation between FcγRIIa H/H or R allele polymorphism and CR (p > 0.05).

Contrary to recent report we showed that FcγRIIa polymorphism is not associated to overall response in patients with DLBCL treated with Rituximab.

No relevant conflicts of interest to declare.