Study on relationships of MS4A1 gene polymorphism with blood concentration and efficacy of rituximab in patients with non-Hodgkin’s lymphoma
- VernacularTitle:非霍奇金淋巴瘤患者MS4A1基因多态性与利妥昔单抗血药浓度及疗效的相关性研究
- Author:
Feng SHI
1
,
2
;
Tao LIU
1
;
He HUANG
1
;
Caifu FANG
1
;
Shaoxing GUAN
2
;
Zhang ZHANG
1
;
Zhao WANG
1
;
Xiaojie FANG
1
;
Zhuojia CHEN
1
;
Shu LIU
1
Author Information
1. Dept. of Pharmacy，Cancer Center，Sun Yat-sen University，Guangzhou 510060，China
2. School of Pharmaceutical Sciences，Sun Yat-Sen University，Guangzhou 510006，China
- Publication Type:Journal Article
- Keywords:
rituximab;
non-Hodgkin’s lymphoma;
MS4A1;
genetic polymorphism;
blood concentration;
efficacy
- From:
China Pharmacy
2025;36(13):1641-1647
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To explore the effects of CD20 coding gene （MS4A1） polymorphism on the blood concentration and efficacy of rituximab in patients with non-Hodgkin’s lymphoma. METHODS A prospective observational study was conducted on 160 newly diagnosed non-Hodgkin’s lymphoma patients who received the R-CHOP regimen at the Sun Yat Sen University Cancer Center from January 2016 to December 2020， with a minimum follow-up period of approximately 5 years. The blood concentration of rituximab was detected by enzyme-linked immunosorbent assay. MS4A1 tagSNPs were selected by Haploview4.2 software， including rs1051461， rs17155034， rs4939364， and rs10501385. The genotype of MS4A1 was detected by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Univariate linear regression analysis was employed to examine the correlation between various factors（demographic， clinical， and genotypic variables） in patients and the steady-state trough concentration of rituximab during the first course of treatment， followed by multivariate linear regression analysis. Kaplan-Meier curves were drawn to evaluate progression-free survival （PFS） and overall survival （OS）. Using MS4A1 genotype and tumor stage as independent variables， Cox regression model was employed to evaluate the factors influencing patient prognosis. RESULTS The blood concentration of rituximab in MS4A1 rs10501385 CC carriers was 15.20 μg/mL，which was significantly lower than 21.95 μg/mL in AA+AC carriers （P＜0.05）. The multivariate linear regression model incorporating tumor stage and MS4A1 rs10501385 polymorphism explained 7.3% of the interindividual variability in rituximab concentrations. Compared with MS4A1 rs1051461 CC carriers， CT+TT carriers had significantly prolonged PFS and OS （P＜0.05）. The Cox proportional hazards regression model showed that the MS4A1 rs1051461 CC genotype （HR＝4.406， 95%CI：1.743-11.137， P＜0.05） and tumor Ⅲ&Ⅳ （HR＝3.233， 95%CI： 1.413-7.399， P＜0.05） were independent risk factors for PFS. CONCLUSIONS The tumor staging and MS4A1 rs10501385 polymorphism are key influencing factors for blood concentration of rituximab， and MS4A1 rs1051461 polymorphism significantly affects PFS in non-Hodgkin’s lymphoma patients.
