Infusion-related reactions to rituximab: frequency, mechanisms and predictors

ABSTRACT

Introduction: Rituximab, an anti-CD20 monoclonal antibody (mAb), is indicated in the treatment of B-cell non-Hodgkin lymphomas, chronic lymphoid leukemia, and rheumatoid arthritis. The occurrence of infusion-related reactions (IRR), especially during the first infusion, is one of the main concerns of rituximab, otherwise well tolerated. Although IRR are usually mild to moderate, fatal evolutions have been reported. These reactions are not specific to rituximab and also observed with other compounds, including those recruiting effectors cells. Further studies are required to predict the frequency and severity of such reactions, to avoid life-threatening complications, especially in the first-in-human studies.

Areas covered: This review reports data available to date on the occurrence of IRR induced by rituximab. Then, factors associated with IRR are described, with proposed pathogenic mechanisms of IRR. Finally, different methods to prevent and manage IRR are reported.

Expert opinion: Various factors have been associated with the occurrence and severity of IRR. A predictive model of IRR is of importance to prevent life-threatening IRR or detrimental interruption of rituximab therapy. This model would combine parameters, such as the number of CD20 positive cells and NK cells (CD16 positive), together with the level of CD20 and CD16 expressions, and FCGR3Apolymorphism.

KEYWORDS:

• Rituximab
• infusion related reactions
• adverse events
• cytokine-release syndrome
• monoclonal antibod
• immunotherapy

Article Highlights

• IRR are one of the main adverse events on rituximab therapy, which is otherwise well tolerated.

• IRR are usually mild to moderate and easily manageable but severe, potentially life-threatening IRR, occur in 10% of patients

• Urgent management of IRR is required to avoid fatal evolution

• The identification of predictive factors for occurrence and severity of IRR is warranted as IRR mainly occur during the first infusion

• Subcutaneous route of rituximab does not circumvent the IRR issue, as the first infusion is still administrated intravenously.

Declaration of interest

G Cartron has been a consultant Celgene and Roche, and received honoraria from Gilead, Jansen, and Sanof. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.