淋巴瘤患者利妥昔单抗药物不良反应的发生与血药浓度的关系的研究

Study on the relationship between the occurrence of adverse drug reactions of rituximab and its blood concentration in lymphoma patients

目的研究利妥昔单抗的药物浓度与药物不良反应的相关性。方法入组130例初治且接受R-CHOP方案一线化疗的患者,其中弥漫大B细胞淋巴瘤患者88例,滤泡淋巴瘤患者35例,粘膜相关淋巴组织淋巴瘤患者7例。观察患者治疗期间利妥昔单抗相关药物不良反应发生情况,并检测利妥昔单抗血药浓度,分析药物浓度与药物不良反应的相关性。通过Logistic回归分析筛选肺炎的高危因素。结果利妥昔单抗相关药物不良反应输液反应、疱疹、肺炎、发热、肝损伤、腹泻的发生率分别为1.54%,2.31%,28.46%,8.46%,1.54%和4.62%。另有皮疹、甲状腺功能减退、眼压升高各1例。分别检测了患者利妥昔单抗第一疗程谷浓度、峰浓度与第四疗程谷浓度,但以上各药物不良反应发生与未发生组患者的利妥昔单抗浓度均无差异。对肺炎进行Logistic回归分析,年龄≥60岁患者肺炎发生风险显著增加(OR=2.79,95%CI:1.24~6.28,P<0.05)。结论经规范预处理,利妥昔单抗相关药物不良反应发生率低,且与药物浓度暂无相关性,年龄≥60岁是患者发生肺炎的高危因素,应注意防范。

Objective To explore the association between rituximab concentration and its drug adverse reactions.Methods A total of 130 newly diagnosed patients receiving R-CHOP as first-line chemotherapy regimen were enrolled,including 88 patients with diffuse large B-cell lymphoma,35 patients with follicular lymphoma,and 7 patients with mucosa-associated lymphoid tissue lymphoma.The incidences of drug adverse reactions related to rituximab during treatment were observed,the concentration of rituximab was detected,and the association between the drug concentration and adverse drug reactions was analyzed.The risk factors of pneumonia were screened by logistic regression analysis.Results The incidences of rituximab related adverse drug reactions infusion reactions,herpes,pneumonia,fever,liver injury,and diarrhea were 1.54%,2.31%,28.46%,8.46%,1.54%and 4.62%,respectively.In addition,three patients experienced a rash,hypothyroidism,and elevated intraocular pressure,respectively.The trough and peak rituximab concentration in the first cycle and the trough concentration in the fourth cycle were detected,but no significant difference was observed in the rituximab concentration in the patients with and without adverse drug reactions.Logistic regression analysis showed that the risk of pneumonia was significantly increased in patients over 60 years old(OR=2.79,95%CI:1.24-6.28,P<0.05).Conclusion Under standard pretreatment,the incidence of rituximab related adverse drug reactions was low,and was not associated with the concentration of rituximab.An age over 60 year old was a high risk factor for pneumonia,so more attention was needed for these patients.