Comparison of Subcutaneous Versus Intravenous Administration of Rituximab As Maintenance Treatment for Follicular Lymphoma: Results From a Two-Stage, Phase IB Study

Abstract

The fixed dose of 1,400 mg SC rituximab predicted by using stage 1 results was confirmed to have noninferior Ctrough 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.

A Canadian Perspective on the Subcutaneous Administration of Rituximab in Non-Hodgkin Lymphoma

“…Growing evidence supports the idea that body weight has minimal influence on the variability of exposure to monoclonal antibodies 6 . In addition, prior studies have reported no dose-limiting toxicities for rituximab up to 5000 mg, suggesting that patients with a low body surface area (bsa) should not experience dose-limiting toxicities 8 .…”

“…To overcome that barrier, the sc formulation of rituximab is highly concentrated to reduce the volume to 11.7 mL and contains 8-recombinant human hyaluronidase alfa, an enzyme that temporarily degrades the extracellular matrix to facilitate the absorption of large volumes 5,6 . The degradation of the extracellular matrix is temporary and allows for the injection of rituximab with minimal tissue distortion, edema, or tissue irritation 5 .…”

“…The sc formulation of rituximab is therefore amenable to a fixed dose, allowing for more convenient dose preparation, with fewer errors. To obtain clinical activity comparable to that of the IV formulation, a pharmacokinetic bridging approach was taken, with the idea that the C trough concentration is related to the saturation of CD20 receptors, which is necessary for optimal efficacy 6 . Therefore, the correct dose of the sc formulation would be that which achieves at least the same pharmacokinetic profile as the IV formulation.…”

“…The phase ib SparkThera trial used a 2-stage design to examine the pharmacokinetics and safety of the sc compared with the IV formulation of rituximab as maintenance therapy for follicular lymphoma (Table i) 6 . In the first stage, 124 patients were randomly assigned to sc rituximab at various doses based on bsa or to IV rituximab at the standard dose of 375 mg/m 2 .…”

“…To date, studies have shown that the safety profiles of the sc and IV formulations of rituximab are similar (Table i) 6,[9][10][11]13,14,16,17 ; however, studies have reported greater rates of gastrointestinal toxicities with the IV formulation (55% vs. 31%) 14 and of local administration-related reactions (arrs) with the sc formulation 6,9-11,13,14,17 . Of patients given the sc formulation, arrs were reported by 31%-50%; of those given the IV formulation, 4% -32% reported such reactions.…”