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Correlation of FcγRIIIa Polymorphisms to the Response of Rituximab in Thai Patients with Diffuse Large B-Cell Lymphoma

Naruemol Angsirisak MSc*, Supeecha Wittayalertpanya MSc**, Wacharee Limpanasithikul PhD**, Udomsak Bunworasate MD***, Danai Owattanapanich MD***

Affiliation : * Interdepartmental Program of Pharmacology, Graduate School, Chulalongkorn University, Bangkok, Thailand ** Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand *** Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

Background : Rituximab is an anti-CD20 chimeric antibody widely used in combination with CHOP regimen for the treatment of diffuse large B-cell lymphoma (DLBCL). It is suggested that this antibody destroys B lymphoma cells mainly by antibody dependent cellular cytotoxicity (ADCC) mechanism via the binding of the drug to FC gamma IIIa receptor (FcγRIIIa) on natural killer (NK) cells, affected to kill cancer cells. The FcγRIIIa has genetic polymorphism at nucleotide position 559 (G559T or V158F or rs396991) have shown influence on the binding and efficacy of rituximab.
Objective : We identified the distribution of FcγRIIIa polymorphism in Thai patients with DLBCL and investigated the correlation between FcγRIIIa polymorphisms and the clinical outcomes in Thai DLBCL patients who were treated with rituximab plus CHOP chemotherapy regimen. Material and Method: The Taqman SNP real-time PCR assay was used to identify the FcγRIIIa polymorphism in the present study and the clinical outcomes of these patients were evaluated and correlated between FcγRIIIa polymorphism.
Results : The distribution of FcγRIIIa genotype in patients were 54.17% homozygous V/V, 10.41% homozygous F/F, and 35.42% heterozygous V/F, and there was no differences in clinical response among these patients (p-value = 0.31). Complete response was assessed in V/V 84.62%, V/F 88.24%, and F/F 80.00%. Partial response was in V/V 7.68% and F/F 20.00%. Stable disease was in V/F 11.76%, progressive disease in V/V 7.72%.
Conclusion : The correlation could not be found between FcγRIIIa polymorphisms to the response of rituximab in Thai patients with diffuse large B-cell lymphoma.

Keywords : Anti CD20, FcγRIIIa polymorphism, Rituximab, Diffuse large B-cell lymphoma


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