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

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's regression was used to assess association with overall survival.

Results: For 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 versus 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 receiving 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).

Figures

Figure 1.

(A) Overall survival (OS) by FCGR3A genotype for the chemotherapy only trial, S8809. (B) Overall survival (OS) by FCGR3A genotype for the chemotherapy + mAb trials, S9800 and S9911 (B). Kaplan-Meier curves, with follow up truncated at ten years. 158 F/F (unfavorable) genotype denoted by solid line; 158 V/F genotype denoted by dotted line; 158 V/V genotype denoted by dashed line.

Figure 2.

(A) Progression-free survival (PFS) by FCGR3A 158 genotype for the chemotherapy only trial, S8809. (B) Progression-free survival (PFS) by FCGR3A 158 genotype for the chemotherapy + mAb trials, S9800 and S9911. Kaplan-Meier curves, with follow up truncated at ten years. 158 F/F (unfavorable) genotype denoted by solid line; 158 V/F genotype denoted by dotted line; 158 V/V genotype denoted by dashed line.