title: Genetic polymorphism of the inhibitory IgG Fc receptor FcgammaRIIb is not associated with clinical outcome in patients with follicular lymphoma treated with rituximab.
abstract: Polymorphisms of activating FcgammaRIIIa (CD16) and FcgammaRIIa (CD32a) have been found to predict rituximab response, probably because of the relative efficiency of different FcgammaR variants in performing antibody-dependent cellular cytotoxicity. The inhibitory FcgammaRIIb (CD32b) has an opposing effect on effector cells. Here, we examined whether an FcgammaRIIb 232 isoleucine (I)/threonine (T) polymorphism predicts rituximab response in 101 patients with follicular lymphoma. Eighty-four patients were 232 I/I, 15 were 232 I/T and two were 232 T/T. The response rate was similar among the three groups. The 2-year progression free survival (PFS) and median time to progression (TTP) were not different between I/I and I/T groups. The TTP was not determined in T/T group because of small number of patients. The FcgammaRIIIa 158 V/V and FcgammaRIIa 131 H/H genotypes continued to emerge as independent predictors for higher response rate and longer TTP. This study is the first to determine whether inhibitory FcgammaRIIb play a role in rituximab's anti-tumor effect in humans.
authors.affiliation: Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. wkweng@stanford.edu
authors.forename: Wen-Kai
authors.initials: WK
authors.lastname: Weng
authors.forename: Ronald
authors.initials: R
authors.lastname: Levy
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D008224:Lymphoma, Follicular / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics / Q000379:methods; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011379:Prognosis; D017452:Receptors, IgG / Q000235:genetics*; D012189:Retrospective Studies; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C080571:Fc gamma receptor IIB; D017452:Receptors, IgG; D000069283:Rituximab