Rituximab exposure-response in triweekly R-CHOP treatment in DLBCL: A loading dose is recommended to improve clinical outcomes.

Previous exposure-response analyses for rituximab suggest that higher rituximab concentrations were associated with an improvement in efficacy, however, clinical studies investigating a higher rituximab dose had mixed results. To further explore the exposure-response relationship of rituximab, a prospective observational analysis was performed involving 121 newly diagnosed diffuse large B-cell lymphoma patients treated with triweekly R-CHOP. The trough concentration in the first cycle (C1-trough ) was significantly higher in patients achieving complete remission (CR) compared to patients that did not achieve complete remission (22.00 μg/mL vs. 16.62 μg/mL, P=0.0016), however, this difference between the two groups disappeared in later cycles. The relationship between rituximab C1-trough and achieving a CR was confirmed by matched-pair logistic regression analysis (OR, 0.79; P = 0.0020). In addition, a higher C1-trough (≥18.40 μg/mL) was associated with longer progression-free survival (P 18.40 μg/mL. Disease stage was found to be the most significant influencing factor of C1-trough , with 51.02% of patients at stage IV with an observed C1-trough <18.40 μg/mL. For these advanced patients, population pharmacokinetic (PK) simulations using an established model suggest that a loading dose of 800 mg/m2 may help to improve clinical outcomes.