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

Ann Oncol. 2008 Aug;19(8):1485-1487. doi: 10.1093/annonc/mdn163. Epub 2008 Apr 11.

Abstract

Background: Neutrophils could play an important role in in vivo rituximab anti-lymphoma activity. FcgammaRIIIb is expressed only by neutrophils and FcgammaRIIIb-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, FcgammaRIIIb-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% homozygous for 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Agents / therapeutic use*
  • Female
  • GPI-Linked Proteins
  • Humans
  • Lymphoma, Follicular / drug therapy*
  • Lymphoma, Follicular / genetics
  • Lymphoma, Follicular / immunology*
  • Male
  • Neutrophils / drug effects
  • Neutrophils / immunology*
  • Polymorphism, Genetic
  • Receptors, IgG / genetics*
  • Receptors, IgG / immunology
  • Rituximab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Agents
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Receptors, IgG
  • Rituximab