Subcutaneous rituximab 1600 mg, in combination with fludarabine and cyclophosphamide, achieved trough serum concentrations that were pharmacokinetically equivalent to those achieved with intravenous rituximab 500 mg/m2, a study published in the journal The Lancet Haematology has shown.1
The safety and efficacy profiles were also similar between the 2 regimens.
For the phase 1b trial, researchers sought to confirm the pharmacokinetic non-inferiority of subcutaneous rituximab as compared with intravenous rituximab, and evaluate its safety and efficacy.
Researchers enrolled 176 adult patients with previously untreated chronic lymphocytic leukemia (CLL). Patients were randomly assigned 1:1 to receive rituximab 1600 mg subcutaneously or rituximab 500 mg/m2 intravenously, plus fludarabine and cyclophosphamide, every 4 weeks for up to 6 cycles. All patients received rituximab 375 mg/m2 intravenously in cycle 1.
Results showed that the geometric mean trough serum concentration at cycle 5 in patients who received subcutaneous rituximab was non-inferior to that in patients given intravenous rituximab (97.5 μg/mL vs 61.5 μg/mL).
In terms of safety, a similar proportion of patients between the 2 treatment arms reported experiencing treatment-related adverse events. Grade 3 or higher neutropenia occurred in 56% of patients in the subcutaneous group and 52% of those in the intravenous group. Serious febrile neutropenia was reported in 11% and 4%, respectively.
Researchers also found that a comparable proportion of patients experienced infusion-related reactions; however, there were differences in the rate of injection-site erythema and nausea. Injection site erythema was more common in the subcutaneous group, whereas nausea was more common in the intravenous arm.
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“Treatment with subcutaneous rituximab should allow patients with CLL to receive clinical benefit from the drug via a more convenient delivery method than the intravenous route, and might also be used in combination regimens with approved and emerging oral regimens,” the authors concluded.
- Assouline S, Buccheri V, Delmer A, et al. Pharmacokinetics, safety, and efficacy of subcutaneous versus intravenous rituximab plus chemotherapy as treatment for chronic lymphocytic leukaemia (SAWYER): a phase 1b, open-label, randomised controlled non-inferiority trial. Lancet Haematol. 2016;3(3):e128-e138.