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 FcγRIIIa (CD16) and FcγRIIa (CD32a) have been found to predict rituximab response, probably because of the relative efficiency of different FcγR variants in performing antibody-dependent cellular cytotoxicity. The inhibitory FcγRIIb (CD32b) has an opposing effect on effector cells. Here, we examined whether an FcγRIIb 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 FcγRIIIa 158 V/V and FcγRIIa 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 FcγRIIb play a role in rituximab's anti-tumor effect in humans.

Keywords:

• Follicular lymphoma
• rituximab
• FcγR
• polymorphism
• antibody-based immunotherapy
• lymphoma and Hodgkin disease
• immunotherapy