Infusion Rate Escalation Study of Rituximab in Patients with CD20+ B-Cell Lymphomas: A Single Institution Analysis in Japan

Background. To determine the maximum tolerable infusion rate of rituximab, and investigate the safety and feasibility of rapid infusion of rituximab for patients with CD20 positive B-cell lymphomas (CD20+NHL). Patients and Methods. 18 patients with CD20+NHL were registered. This study had six cohorts of administration rate of rituximab. The median age was 56 years (range, 38–79), and five of 18 patients were male. Two patients (11%) with diffuse large B-cell lymphoma were receiving R-CHOP therapy, two (11%) with indolent lymphoma were receiving R-CVP therapy, and 14 (78%) with indolent lymphoma were receiving rituximab as maintenance therapy. Results. A total of 88 cycles of rituximab was administered. Rapid infusion of rituximab was well tolerated, with only one grade 3 leukocytepenia and one grade 4 neutropenia. Four patients (22%) developed grade 1 infusion-related toxicities at the first administration of rituximab. No patient with severe drug-related events was observed. Conclusions. We determined that the maximum tolerable infusion rate of rituximab is 300？mL/h (under 700？mg/h), and confirmed that administration of over 60 minutes is safe and feasible. We recommend rapid administration of rituximab for practice setting in patients with CD20+NHL being treated with rituximab or rituximab-containing chemotherapy. (Clinical trial no. JFCR2009-1027). 1. Introduction Rituximab, a chimeric murine/human IgG kappa monoclonal antibody, has been developed against CD20+ B-cell lymphomas (CD20+NHL) [1]. Adding rituximab to chemotherapy is standard therapy for patients with CD20+ aggressive and indolent B-cell lymphomas (CD20+NHL) and, more recently, as maintenance therapy after response to induction therapy for indolent B-cell lymphoma [2–5]. Despite the improved outcome with the addition of rituximab to chemotherapy, its administration can be associated with infusion-related toxicities such as fever, rash, urticaria, dyspnea, bronchospasms, hypertension, hypotension, or other allergic reactions/hypersensitivities. Infusion-related reactions can occur in approximately one-fourth of patients receiving the first administration of rituximab. Recommendations to reduce the incidence of these reactions include the administration of rituximab over a prolonged period, usually 5-6 hours for the first infusion and 3-4 hours for subsequent infusions. Recently, several investigators have reported that rapid infusion of rituximab, for approximately 60–90 minutes, is a safe administration schedule for the patients with CD20+NHL [6–11]. However, it is unclear what would