Rituximab serum concentrations during immuno-chemotherapy of follicular lymphoma correlate with patient gender, bone marrow infiltration and clinical response

Background Treatment of follicular lymphoma with ritumab is currently recommended at a dose of 375 mg/m(2). We aimed to provide a rational for optional dosing and scheduling of this anti-CD20 antibody based on pharmacokinetics. Design and Methods Clinical efficacay of immuno-chemotherapy with rituximab, fludarabine and mitoxantrone followed by 2-monthly rituximab maintenance was evaluated in 29 patients with previously untreated follicular lymphoma in a prospective phase II trial (AGMT-NHL9). Pharmacokinetic analysis was assessed in 17 patients. Results Induction treatment resulted in high clinical reposonse rates (complete remission 66%; ORR 100%). Significantly higher complete remission rates were observed in female patients (86 vs. 47%; Odds Ratio 6.8, 95% CI: 1.12; 41.82; P=0.05). Rituximab pharmacokinetic analysis showed a high variability ranging over almost 1 order of magnitude at maintenance cycle 1 (area under the curve 1,540-12,025 g/L*days). Median area under the curve was lower in men (81%) and in patients with initial bone marrow infiltration (76%). Higher rituximab serum concentrations before next therapy (C-trough) were associated with female sex (P=0.04) as well as with absence of initial bone marrow infiltration (P=0.001). C-trough correlated with remission quality (complete vs. partial remission; P=0.005) and progression-free survival (P=0.03). A decline in rituximab Ctrough below 25,000 ng/mL was observed 9.5 to 62 month before clinical relapse (P=0.008). Conclusions The result of this pilot trial suggest that more differentiated dosing schedules based on gender and bone marrow infiltration should be explored for rituximab theraphy for lymphoma. This study was registered in ClinicalTrials.gov (Identifier: NCT01560117).