Phase III safety study of rituximab administered as a 90-minute infusion in patients with previously untreated diffuse large B-cell and follicular lymphoma

Abstract

This phase III, multicenter, single-arm trial investigated the impact of 90 min rituximab infusions on infusion-related reactions (IRRs) in patients with untreated diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL). Patients received six or eight cycles of rituximab plus cyclophosphamide, vincristine, doxorubicin and prednisone for DLBCL or plus cyclophosphamide, vincristine and prednisolone for FL. A total of 425 patients received the first rituximab infusion per standard guidelines; median duration 240 min. Patients who did not experience grade ≥ 3 IRRs received subsequent infusions over 90 min (363 patients). A total of 303 patients received ≥ 6 cycles of rituximab. Fifty-three patients withdrew after cycle 1; 10 for grade 3 or 4 IRRs and one for a grade 3 adverse event. During cycle 2, 139 patients had IRRs, including four grade 3 IRRs. A 90 min rituximab infusion is well tolerated and feasible for patients with DLBCL or FL who tolerate the first standard rate infusion.

Subcutaneous Rituximab for the Treatment of B-Cell Hematologic Malignancies: A Review of the Scientific Rationale and Clinical Development

“…Rituximab was initially formulated for administration via IV infusion, with infusions typically administered over a period of 1.5–6 h [ 7 , 27 ]. The first infusion is usually the longest, to minimize the risk of infusion-related reactions (IRRs), with subsequent infusions being given at slightly more rapid rates.…”

“…IRRs are reported by most patients during their first infusion (77%) [ 7 ], but decrease substantially with subsequent infusions, and cytokine release syndrome accompanied by hypotension and bronchospasm is reported in 10% of patients [ 7 ]. In recent years, a 90-min infusion schedule for second and subsequent infusions has proven to be feasible and safe [ 27 ].…”

Rituximab Faster Infusion for Patients With Non-Hodgkin's Lymphoma in the United States

“…There is evidence, however, that before implementing a faster infusion administration schedule, some large academic cancer centers are awaiting data from the RATE trial, a prospective, open-label, Phase III, multicenter, singlearm trial designed to assess the safety, pharmacokinetics, and pharmacodynamics of faster infusion of rituximab in previously untreated patients with diffuse large B-cell lymphoma and follicular NHL. 17 Data from the RATE trial led to the October 19, 2012 US Food and Drug Administration approval of a 90-minute infusion for rituximab starting at Cycle 2 for previously untreated follicular NHL and diffuse large B-cell lymphoma patients who did not experience a Grade 3 or 4 infusion-related adverse reaction during Cycle 1. The primary objective of this study was to determine the incidence of Grade 3 or 4 infusionrelated reactions resulting from faster infusion of rituximab in patients who have previously received rituximab at the standard infusion rate as stated in the USPI without experiencing a Grade 3 or 4 infusionrelated adverse event.…”

Safety, tolerability and pharmacokinetics of shorter duration of infusion of obinutuzumab in Japanese patients with B-cell non-Hodgkin lymphoma: final results of the phase II GATS study

“…The main potential disadvantage of a shorter duration of infusion (SDI) lies in the possibility of increased risk of infusion-related reactions (IRRs) mediated by cytokine release ( 9 , 10 ). However, studies in patients with rheumatoid arthritis or B-cell NHL have shown reduction of rituximab infusion times from at least 4 h to 1.5–2 h to be feasible ( 8 , 11 ), which has in turn led to the recommendation to increase infusion rates for rituximab ( 12 ) and, similarly, to the investigation of SDI in patients receiving obinutuzumab.…”