Acute adverse reactions of rapid Rituximab infusion among adult patients with Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia.

Background: Rapid Rituximab infusion has become increasingly popular globally. Although pharmaceutical manufacturers recommend second and subsequent infusions to run over 2-3 hours, many cancer centres have changed their clinical practice based on their own research and the results from other primary studies. Such research studies claim that it is safe to administer Rituximab rapidly among cancer patients especially in Non Hodgkin Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL). In addition, the studies suggest that the rapid infusion of Rituximab also results in benefits of cost saving and better resource utilisation. However, these studies have not been critically appraised for their validity and application to the global population. No previous systematic reviews on this topic have been identified.Objective The objective of this review was to critically appraise, synthesise and present the best available evidence related to the safety of rapid Rituximab infusion among adult patients with NHL and CLL.

Inclusion Criteria: The participants of interest were adults aged 18 years old and above who had a diagnosis of NHL or CLL at any stage, have had prior exposure to Rituximab and received Rituximab with or without combination of any chemotherapy.The intervention of interest was rapid Rituximab infusion to be completed in 120 minutes or less.The studies of interest were both experimental and non-experimental studies.The primary outcomes of interest were the presence of acute adverse reactions and their severity. The secondary outcomes of interest were the management of the acute adverse reactions and patient mortality rate resulting from adverse reactions.Search strategy The search sought to identify published and unpublished studies from 1997 till 2010. A three-step search strategy was used for electronic databases, grey literature and reference lists.Methodological quality Two independent reviewers used the standard critical appraisal tool from JBI-MAStARI to assess the methodological qualities of the studies that matched with inclusion criteria.Data collection A standard data form from JBI-MAStARI was used to extract the data across all included studies.Data synthesis Proportional Meta-analysis based on DerSimonian-Laird weights for the random effects model was used for statistical pooling through Stats Direct. Heterogeneity was assessed using Cochran Q. When statistical pooling is not possible, the findings are presented in narrative summary.

Results: A total of 753 patients were included in this review. All except one patient completed a total of 2298 cycles of rapid Rituximab infusions. Seventeen and one acute adverse reactions were reported among NHL and CLL patients respectively. There were five reactions which were not clearly stated if they were occurring in NHL or CLL patients. All were mild to moderate reactions except one patient developed severe reaction and withdrew from the study.

Conclusions: Rapid Rituximab infusion is safe for NHL patients especially in a 90-minute regimen. However, rapid rituximab infusion is not recommended for CLL patients due to lack of evidence.

Implications For Practice: 90-minute rapid Rituximab infusion with or without steroid premedication is recommended for NHL patient at second and subsequently infusions. No recommendations can be made in relation to stage of disease or the presence of bulky disease or leucocytosis. It is not recommended, based on the current evidence, to use rapid Rituximab for CLL patients.

Implications For Research: Further research is needed on the role of monoclonal antibodies development in rapid infusion, especially in the second and subsequent cycles. Currently, this review broadly establishes that rapid Rituximab infusion over 90 minutes is safe for NHL patients. However, more research and detailed analysis is needed to develop more specific guidelines.