性别和年龄对利妥昔单抗治疗弥漫大B细胞淋巴瘤患者的影响研究

Effect of gender and age on rituximab therapy for diffuse large B-cell lymphoma

目的 拟通过血药浓度监测验证并探索相关机制,以指导利妥昔单抗个体化的剂量调整。方法 开展前瞻性临床试验入组99例初治的弥漫大B细胞淋巴瘤(DLBCL)患者,以酶联免疫法检测利妥昔单抗浓度,分析药物浓度与疗效的相关性,及年龄、性别、肿瘤分期对浓度和疗效的影响。结果 R-CHOP方案一线化疗的响应率高达82.83%,半年、1年肿瘤进展率分别为11.11%和15.15%,利妥昔单抗谷浓度的均值为(21.00±8.12)μg·mL^(-1)。年龄≥70岁患者1年肿瘤进展率显著增高至60.00%,患者利妥昔单抗谷浓度均值显著降低至(13.37±6.69)μg·mL^(-1)。男性患者1年肿瘤进展率显著增高至21.82%,患者利妥昔单抗谷浓度对比女性有降低趋势。肿瘤分期Ⅳ期患者1年肿瘤进展率显著增高至30.30%,患者药物谷浓度均值显著降低至(17.07±8.93)μg·mL^(-1)。依据患者肿瘤分期、年龄、性别进行分层分析,发现Ⅳ期且年龄≥65的女性、Ⅳ期年龄<65的男性、Ⅳ期年龄≥65的男性1年肿瘤进展率分别为40%,41.67%,50%,显著高于其他患者。同时,3组患者利妥昔单抗谷浓度分别为(13.57±8.43),(17.09±6.50),(10.93±5.98)μg·mL^(-1),显著低于其他患者。结论 肿瘤Ⅳ期且年龄≥65的女性及Ⅳ期男性临床疗效不理想,体内利妥昔单抗浓度较低,推荐适当增加给药剂量。

Objective Some clinical trials have shown that female lymphoma patients receiving rituximab contained regimen benefit more than elderly male patients. The aim of this study was to verify this phenomenon and to explore the relevant mechanism through therapeutic drug monitoring and then to guide the dosage adjustment for rituximab. Methods A prospective clinical trial was conducted and 99 patients with newly diagnosed diffuse large B-cell lymphoma(DLBCL) were enrolled, the concentration of rituximab was detected by enzyme linked immunosorbent assay, and the association between the drug concentration and clinical outcomes, the influence of age, gender and tumor stage on rituximab concentration and outcomes were analyzed. Results The treatment response rate of the first-line R-CHOP regimen was as high as 82.83%;the tumor progression rates for half a year and one year were 11.11% and 15.15, respectively;the mean trough concentration of rituximab was(21.00±8.12) μg·mL. The one-year tumor progression rate of patients ≥70 years was significantly increased to 60. 00% and the trough concentration of patients with aged ≥ 70 years was significantly decreased to( 13. 37 ± 6. 69)μg·mL^(-1)-1. The one-year tumor progression rate of male patients was significantly increased to 21. 82%,and the rituximab concentration of male patients also tended to be lower than that in female patients. The one-year tumor progression rate of patients with stage Ⅳ disease was significantly increased to 30. 30%,and the drug concentration was significantly reduced to( 17. 07 ± 8. 93) μg·mL. A stratified analysis based on the patient’s tumor stage,age,and gender was further conducted,the one-year tumor progression rates of women with Ⅳ stage and age≥ 65,men with stage Ⅳ and age < 65 and men with stage Ⅳ and age ≥65 were 40%,41. 67% and 50%,respectively,which were significantly higher than those in other patients,meanwhile,the trough concentrations of rituximab in the three groups were( 13. 57 ± 8. 43),( 17. 09 ± 6. 50) and( 10. 93 ± 5. 98) μg·mL,respectively,which were significantly lower than those in other patients. Conclusion Therefore,women with Ⅳ stage and age≥ 65 and men with stage Ⅳ all had poor clinical outcome and accompanied with insufficient rituximab concentration,an appropriate increase of rituximab dosage for them was recommended.