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).

• Authors: Daniel O Persky, David Dornan, Bryan H Goldman, Rita M Braziel, Richard I Fisher, Michael Leblanc, David G Maloney, Oliver W Press, Thomas P Miller, Lisa M Rimsza
• Journal: Haematologica (Haematologica) Vol. 97 Issue 6 Pg. 937-42 (Jun 2012) ISSN: 1592-8721 [Electronic] Italy
• PMID: 22271896 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Murine-Derived
• FCGR3A protein, human
• Fc gamma receptor IIA
• Receptors, IgG
• Rituximab
• tositumomab I-131

Topics

• Adult
• Aged
• Antibodies, Monoclonal (administration & dosage, therapeutic use)
• Antibodies, Monoclonal, Murine-Derived (administration & dosage, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Combined Modality Therapy (methods)
• Female
• Genotype
• Humans
• Lymphoma, Follicular (diagnosis, immunology, mortality, therapy)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Prognosis
• Receptors, IgG (genetics)
• Rituximab
• Survival Analysis