title: 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.
  
  
  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).
authors.affiliation: Arizona Cancer Center, University of Arizona, Tucson, AZ 85724-5024, USA. dpersky@azcc.arizona.edu
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Persky
authors.forename: David
authors.initials: D
authors.lastname: Dornan
authors.forename: Bryan H
authors.initials: BH
authors.lastname: Goldman
authors.forename: Rita M
authors.initials: RM
authors.lastname: Braziel
authors.forename: Richard I
authors.initials: RI
authors.lastname: Fisher
authors.forename: Michael
authors.initials: M
authors.lastname: Leblanc
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Press
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Miller
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Rimsza
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D005838:Genotype; D006801:Humans; D008224:Lymphoma, Follicular / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D017452:Receptors, IgG / Q000235:genetics*; D000069283:Rituximab; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C496124:FCGR3A protein, human; C080568:Fc gamma receptor IIA; D017452:Receptors, IgG; D000069283:Rituximab; C119496:tositumomab I-131