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.