Neutrophil role in in vivo anti-lymphoma activity of rituximab: FCGR3B-NA1/NA2 polymorphism does not influence response and survival after rituximab treatment

Abstract

Background: Neutrophils could play an important role in in vivo rituximab anti-lymphoma activity. FcγRIIIb is expressed only by neutrophils and FcγRIIIb-neutrophil antigen (NA)1/NA2 polymorphism influenced phagocytosis of immunoglobulin G1-opsonized particles. We formulated the hypothesis that if neutrophils are critical cells for in vivo rituximab activity, FcγRIIIb-NA1/NA2 polymorphism could influence the response to rituximab. Patients and methods: FCGR3B-NA1/NA2 genotypes were determined in 46 patients having received rituximab for a previously untreated, follicular, non-Hodgkin's lymphoma. The clinical response and the disappearance of the BCL2-JH gene rearrangement in both peripheral blood and bone marrow were evaluated at 2 months (M2) and each year during 7 years. Results: They were 13% homozygous for FCGR3B-NA1, 61% homozygousfor FCGR3B-NA1/NA2 and 26% heterozygous. The objective response rates at M2 were 67% in homozygous FCGR3B-NA1 patients compared with 75% in homozygous FCGR3B-NA2 and 75% in heterozygous patients (not significant). We found no difference for progression-free and overall survival by FCGR3B-NA1/NA2 genotypes. Conclusion: These results indicate no association between FCGR3B-NA1/NA2 polymorphism and response to rituximab indicating no significant role of phagocytosis mediated by neutrophils in in vivo mechanism of rituximab activity. © The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.