Immunoglobulin G Fc Receptor FcγRIIIa 158 V/F Polymorphism Correlates With Rituximab-Induced Neutropenia After Autologous Transplantation in Patients With Non-Hodgkin's Lymphoma

Purpose Rituximab has been given after autologous hematopoietic cell transplantation for recurrent or refractory B-cell lymphoma with the goal of eradicating minimal residual disease. Our previous report showed that administration of two courses of rituximab after transplantation is feasible, with encouraging clinical outcomes after a short follow-up. However, neutropenia after the first or second post-transplantation rituximab treatment occurred in 52% of patients. We previously reported that polymorphisms of two immunoglobulin G Fc receptors predict rituximab response, presumably because of their role in antibody-dependent cellular cytotoxicity. In the current report, we determine whether Fc gamma R polymorphisms are correlated with clinical outcomes in 33 patients with B-cell non-Hodgkin's lymphoma who received post-transplantation rituximab. Patients and Methods Genomic DNA was used for Fc gamma RIIIa V/F or the Fc gamma RIIa H/R genotyping. The Fc gamma R polymorphisms were then correlated with the incidence of rituximab-induced neutropenia, event-free survival (EFS), and overall survival (OS). Results The Fc gamma RIIIa 158 V allele dose was correlated with a higher incidence of rituximab-induced neutropenia. The odds of neutropenia after the first or second post-transplantation rituximab increased three-fold with each V allele (robust z = 2.08, P = .038). The Fc gamma RIIa polymorphism had no impact on rituximab-induced neutropenia. We did not observe a correlation of either Fc gamma RIIIa or Fc gamma RIIa polymorphism with EFS or OS. Conclusion The high affinity Fc gamma RIIIa 158 V allele is associated with rituximab-induced neutropenia after autologous transplantation. This is a potential tool to identify a high-risk population for developing neutropenia after antibody therapy.