Fc Gamma Receptor 3A and 2A Polymorphisms Do Not Predict Response to Rituximab in Follicular Lymphoma.

Area of Science:

• Oncology
• Pharmacogenomics
• Immunotherapy

Background:

• Preclinical data suggest Fc gamma receptor (FCGR) gene single nucleotide polymorphisms (SNPs) may impact rituximab efficacy.
• The clinical significance of these FCGR SNPs in follicular lymphoma (FL) remains uncertain.

Purpose of the Study:

• To investigate the association between FCGR gene SNPs and patient response to rituximab in a prospective cohort of previously untreated, low tumor burden FL patients.
• To determine if FCGR3A and FCGR2A genotypes influence initial response rates and response duration to rituximab therapy.

Main Methods:

• Prospective collection of specimens for SNP genotyping in the rituximab extended schedule or re-treatment (RESORT) study.
• Analysis of 321 consenting patients with FL treated with single-agent rituximab, with responders randomized to maintenance rituximab (MR) or re-treatment (RR).
• Correlation of FCGR3A and FCGR2A genotypes with initial response rates and response duration in patients undergoing rituximab therapy.

Main Results:

• Initial response rate to rituximab was 71%, with no FCGR genotypes predicting initial response.
• In the randomized phase (n=235), response duration was not associated with FCGR3A or FCGR2A genotypes in either the MR or RR arms.
• While initial response and duration showed some correlation with FCGR3A and FCGR2A SNPs, these findings were not significant in the overall analysis.

Conclusions:

• FCGR3A and FCGR2A SNPs do not appear to confer differential responsiveness to rituximab in treatment-naïve, low tumor burden FL patients.
• The clinical utility of FCGR genotyping for predicting rituximab outcomes in this patient population is not supported by this study.
• Further research may be needed to explore other genetic factors influencing rituximab efficacy.