Rapid Infusion Rituximab in Combination with Steroid Containing Chemotherapy Can Be Given Safely and Substantially Reduces Resource Utilization.

Abstract

Background Administration of rituximab, a chimeric anti-CD20 monoclonal antibody, can be associated with substantial infusion-related toxicity, including hypersensitivity reactions causing fever, rash, cardiovascular and respiratory compromise and rarely a fatal cytokine release syndrome. The risk of grade 3/4 infusion reactions is greatest with the first infusion (7%), and lower for all subsequent infusions (2% for fourth infusion). To minimize the risk of reaction, strict guidelines for administration have been developed, requiring lengthy infusion times (average 5–6 h for first infusion and 3–4 h for remaining infusions). As more patients are now receiving rituximab in combination with steroid containing chemotherapy regimens, the risk of reaction may be lower and the need for lengthy infusion unnecessary. Methods In March 2004, we began a pilot study investigating the safety of a rapid infusion rituximab schedule for all patients with non-Hodgkin’s lymphoma receiving rituximab in combination with CHOP or CVP chemotherapy. The schedule of administration for cycle 1 of therapy was unaltered and delivered according to the product monograph. All further cycles were administered the same day of chemotherapy, over a total infusion time of 90 minutes (20% of the dose in the first 30 min then the remaining 80% over 60 min; total dose delivered in 250 mL). Patients took their daily prednisone dose prior to receiving rituximab. Safety information was monitored prospectively using an infusion monitoring record. Results 67 patients have been treated for a total of 163 infusions (median infusions per patient: 2). Patient characteristics are as follows: median age, 64 y (range 21–90); 67% male; 66% stage III/IV; PS > 1, 19%; IPI score high/high-intermediate, 36%. Histology: 42 DLBCL, 6 follicular, 8 transformed, 4 mantle cell, 7 other. No patients had increased numbers of circulating lymphocytes. Chemotherapy regimen: 57 CHOP, 9 CVP, 1 other. The 90-minute rituximab infusion schedule was extremely well tolerated with no grade 3/4 adverse infusion related events observed. One patient developed mild transient asymptomatic hypotension, BP 97/71, grade 1 toxicity, which was managed with a 30-minute infusion delay. Four patients (6%) had an adverse event with their first cycle (administered at the standard rate) and subsequently tolerated the rapid infusion schedule without event. Five patients did not receive steroids with their treatment due to a prior history of hepatitis exposure and none of these patients developed an adverse event with the rapid infusion. The overall rate of grade 3/4 infusion related reactions observed with the rapid infusion protocol was 0% (95% CI 0–0.044), which is at least as low as the expected rate following the standard infusion schedule. No increased incidence in minor reactions was noted. Introduction of this shortened infusion schedule has enabled us to cut rituximab infusion times in half, allowing more patients to be conveniently treated and ensuring that both chemotherapy and rituximab can be given in one rather than two days. Conclusion A rapid (90-minute) rituximab infusion schedule in combination with a steroid containing chemotherapy regimen is well tolerated and safe when administered from the second infusion onward. This shortened infusion schedule has resulted in a substantial reduction in resource utilization.

Safety of rapid rituximab infusion in adult cancer patients: A systematic review

“…Thirty‐nine studies appeared to match the inclusion criteria and were retrieved for detailed examination. Of these, 23 studies were excluded because they were incongruent with the review inclusion criteria 9,12,15–17,23–25,30–44 . Although three clinical trials appeared to match the inclusion criteria, 45–47 they were excluded from this review as no results are available to date.…”

Rapid infusion of rituximab with or without steroid‐containing chemotherapy: 1‐yr experience in a single institution

“…Although the recommended infusion rate for subsequent infusions is up to double that of the first infusion, several groups have investigated faster infusion rates of rituximab to allow a reduction in the total administration time (5–7). Other groups are making modifications to premedication schedules, such as omitting premedication, to test their feasibility.…”

“…Other groups are making modifications to premedication schedules, such as omitting premedication, to test their feasibility. No significant increase in adverse events has been reported with rapid infusion when rituximab is combined with chemotherapy that contains steroids (5). We decided to investigate the feasibility of a rapid infusion of rituximab not only in patients treated with steroid containing chemotherapy but also in patients who were not receiving steroids in their chemotherapy courses.…”

“…These extended infusions cause long stays in day units, which are inconvenient for patients and have significant resource implications. Recently, Sehn et al (5) have suggested that a rapid rituximab infusion schedule in combination with steroid‐containing chemotherapy is safe. The aims of this study were to assess the safety of a rapid infusion of rituximab with or without steroid‐containing chemotherapy schedules and to evaluate the feasibility of this schedule in terms of shortening stays in hospital.…”

Rapid Infusion Rituximab Changing Practice for Patient Care

“…10- 13 The results of our study are comparable with similar studies results that had been published from other institutes. [10][11][12][13] This preliminary data may be used to develop alternative guidelines for administration of rituximab.…”