Low initial trough concentration of rituximab is associated with unsatisfactory response of first-line R-CHOP treatment in patients with follicular lymphoma with grade 1/2

摘要

For follicular lymphoma(FL)with grade 1/2,the complete response(CR)rate of the first-line R-CHOP treatment was significantly low.In this study,we assessed the rationality of the administration of rituximab for FL patients with grade 1/2 based on concentration-response relationship analyses.Thus,we conducted a prospective pharmacokinetic(PK)study in 68 FL patients with grades 1-3 treated with R-CHOP at 21-day intervals.Plasma rituximab concentrations were quantified using ELISA and the population PK modeling was established with Phoenix? NLMETM.The first cycle trough concentration(C1-trough)of rituximab was a significant independent risk factor for achieving CR in matched-pair logistic regression analysis,rather than the concentrations in later cycles;the recommendatory minimum optimal C1-trough was 13.60 μg/mL.Patients with grade 1/2 had significantly lower C1-trough compared with grade 3(12.21 μg/mL vs.23.45 μg/mL,P＜0.001),only 30％patients with grade 1/2 could reach 13.60μg/mL,compared with 91.67％in patients with grade 3,which was in accord with its unsatisfactory CR rates(4333％vs.76.32％).The stage indicating the tumor burden(the target)was a crucial influence factor for C1-trough,accounting for 40.70％of its variability,70％patients with grade 1/2 were stage Ⅳ in this study,since the systemic therapy only started at the disseminated disease stage.The initial dose of 1800 mg was recommended by Monte Carlo simulation for patients with grade 1/2.In summary,low C1-trough accounted for low-grade FL's unsatisfactory CR rate,designing the first dosage of rituximab should be a very important component of individualized therapy for FL.