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

Antonio Salar, Irit Avivi, Beate Bittner, Reda Bouabdallah, Mike Brewster, Olivier Catalani, George Follows, Andrew Haynes, Florence Hourcade-Potelleret, Andrea Janikova, Jean François Larouche, Christine McIntyre, Michael Pedersen, Juliana Pereira, Pakeeza Sayyed, Ofer Shpilberg, Gayane Tumyan

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

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 (Ctrough) 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 Ctrough 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 Ctrough 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:Ctrough 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 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.

Original languageEnglish
Pages (from-to)1782-1791
Number of pages10
JournalJournal of Clinical Oncology
Volume32
Issue number17
DOIs
StatePublished - 10 Jun 2014
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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