Comparison of subcutaneous versus intravenous administration of rituximab as maintenance treatment for follicular lymphoma: Results from a two-stage, phase IB study

Purpose: This two-stage phase IB study investigated the pharmacokinetics and safety of subcutaneous (SC) versus intravenous (IV) administration of rituximab as maintenance therapy in follicular lymphoma. Patients and Methods: In stage 1 (dose finding), 124 patients who responded to rituximab induction were randomly assigned to SC rituximab (375 mg/m², 625 mg/m ², or an additional group at 800 mg/m²) or IV rituximab (375 mg/m²). The objective was to determine an SC dose that would yield a rituximab serum trough concentration (C_trough) in the same range as that of IV rituximab. In stage 2, 154 additional patients were randomly assigned (1:1) to SC rituximab (1,400 mg) or IV rituximab (375 mg/m ²) given at 2- or 3-month intervals. The objective was to demonstrate noninferior rituximab C_trough of SC rituximab relative to IV rituximab 375 mg/m². Results: Stage 1 data predicted that a fixed dose of 1,400 mg SC rituximab would result in a serum C_trough in the range of that of IV rituximab. Noninferiority (ie, meeting the prespecified 90% CI lower limit of 0.8) was then confirmed in stage 2, with geometric mean C _trough SC:C_{trough IV} ratios for the 2- and 3-month regimens of 1.24 (90% CI, 1.02 to 1.51) and 1.12 (90% CI, 0.86 to 1.45), respectively. Overall safety profiles were similar between formulations (in stage 2, 79% of patients experienced one or more adverse events in each group). Local administration-related reactions (mainly mild to moderate) occurred more frequently after SC administration. Conclusion: The fixed dose of 1,400 mg SC rituximab predicted by using stage 1 results was confirmed to have noninferior C_trough levels relative to IV rituximab 375 mg/m² dosing during maintenance, with a comparable safety profile. Additional investigation will be required to determine whether the SC route of administration for rituximab provides equivalent efficacy compared with that of IV administration.