Angsirisak Naruemol, Wittayalertpanya Supeecha, Limpanasithikul Wacharee, Bunworasate Udomsak, Owattanapanich Danai
J Med Assoc Thai. 2015 Dec;98(12):1215-21.
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.
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.
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.
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%.
The correlation could not be found between FcγRIIIa polymorphisms to the response of rituximab in Thai patients with diffuse large B-cell lymphoma.
利妥昔单抗是一种抗CD20嵌合抗体，广泛用于联合CHOP方案治疗弥漫性大B细胞淋巴瘤（DLBCL）。有研究表明，该抗体主要通过抗体依赖性细胞毒性（ADCC）机制，即药物与自然杀伤（NK）细胞上的FcγIIIa受体（FcγRIIIa）结合，影响杀伤癌细胞，从而破坏B淋巴瘤细胞。FcγRIIIa在核苷酸位置559处存在基因多态性（G559T或V158F或rs396991），已显示对利妥昔单抗的结合和疗效有影响。
我们确定了泰国DLBCL患者中FcγRIIIa多态性的分布，并研究了FcγRIIIa多态性与接受利妥昔单抗联合CHOP化疗方案治疗的泰国DLBCL患者临床结局之间的相关性。
本研究采用Taqman SNP实时PCR检测法鉴定FcγRIIIa多态性，并评估这些患者的临床结局，分析FcγRIIIa多态性之间的相关性。
患者中FcγRIIIa基因型分布为：纯合子V/V占54.17%，纯合子F/F占10.41%，杂合子V/F占35.42%，这些患者的临床反应无差异（p值 = 0.31）。V/V组完全缓解率为84.62%，V/F组为88.24%，F/F组为80.00%。V/V组部分缓解率为7.68%，F/F组为20.00%。V/F组疾病稳定率为11.76%，V/V组疾病进展率为7.72%。
在泰国弥漫性大B细胞淋巴瘤患者中，未发现FcγRIIIa多态性与利妥昔单抗反应之间存在相关性。
