Fc gamma receptor 3a genotype predicts overall survival in follicular lymphoma patients treated on SWOG trials with combined monoclonal antibody plus chemotherapy but not chemotherapy alone.

Publication Type:

Journal Article

Source:

Haematologica, Volume 97, Issue 6, p.937-942 (2012)

Keywords:

2012, Center-Authored Paper, Clinical Research Division, Consortium Authored Paper, February 2012, Public Health Sciences Division

Abstract:

Background:Fc gamma receptor polymorphisms were linked to outcome in follicular lymphoma patients treated with single-agent rituximab, an anti-CD20 monoclonal antibody. In particular, 158F/F genotype of Fc gamma receptor 3A and 131R/R genotype of Fc gamma receptor 2A correlated with worse outcome compared to high-affinity 158V/V and 131H/H, respectively. We examined this association in the context of anti-CD20 monoclonal antibody combined with chemotherapy, as compared to chemotherapy alone, in follicular lymphoma patients treated on SWOG clinical trials.Design and Methods:Tissue from 142 SWOG patients treated with chemotherapy alone (protocol S8809, N=70) or combined chemotherapy and anti-CD20 monoclonal antibody (rituximab and Iodine I-131 tositumomab on protocols S9800 and S9911, N=30 and 42, respectively) was analyzed. DNA was extracted and assayed for Fc gamma receptor 3A V158F and 2A R131H polymorphisms using a TaqMan SNP assay. Stratified Cox regression was used to assess association with overall survival.Results:D. Persky et al. FRGR3A genotype predicts OS in FL treated with chemo + mAbFor Fc gamma receptor 3A there was an association with overall survival in the combination therapy trials but not in the chemotherapy-only trial. Having at least one Fc gamma receptor 3A V allele was associated with improved overall survival vs. F/F (HR = 0.33 (95% CI, 0.11, 0.96), p=0.042). For overall survival, there was evidence of a statistical interaction between the use of mAb and the number of V alleles (0, 1, or 2) (p=0.006), There was no such association for Fc gamma receptor 2A.Conclusions:Fc gamma receptor 3A polymorphism status may be predictive of survival in follicular lymphoma patients given treatments containing an anti-CD20 antibody but not treatment with chemotherapy alone. Thus, Fc gamma receptor 3A polymorphisms may be important to consider in designing new follicular lymphoma trials and new anti-CD20 monoclonal antibodies.(clinicaltrials.gov identifier: NCT00933127).