Clinical and microbiological characteristics of the infections in patients treated with rituximab for autoimmune and/or malignant hematological disorders

Abstract

Introduction: Rituximab is commonly used for the treatment of hematological malignancies and autoimmune diseases. Despite a reputation for good tolerance, case-series and registries reported rituximab-related infections of variable severity including opportunistic infections. We aimed at describing the natural history of infectious events (IE) after treatment by rituximab providing clinical and microbiological features and outcome. Patients and methods: We retrospectively analyzed the medical records of patients treated with rituximab in an internal medicine department of a tertiary hospital between 2007 and 2015, and identified all IE after this therapy. Events' severity was assessed using the Common Terminological Criteria of Adverse Events (version 4.3) definitions. Results: Among 101 patients treated with rituximab, we identified 228 IE in 74 (73.3%) of these patients (median follow-up 30.4 months). Indication for rituximab was either autoimmune disease (AID) (52.5% of patients), or monoclonal hematological disease (MHD) (47.5%). Patients received an overall median number of 5 rituximab infusions [interquartile range: 4–8], representing a cumulative dose of 4340 mg [2620–6160]. After last rituximab infusion, IE occurred after 3.1 months [0.7–9.4]. Respectively, IE were severe in 28.1% of cases in patients treated for AID vs 58.0% in patients treated for MHD (p < 0.001), due to opportunistic pathogens in 7.8% vs 11.0% (p = 0.49) and fatal in 4.7% vs 13.0% (p = 0.044). Factor associated with mortality were polymicrobial infection (p < 0.001), monoclonal hematological disease (p = 0.035), use of steroids over 10 mg/d within the last two weeks (p = 0.003), and rituximab cumulative dose (p < 0.001). We identified a group of 10 patients (9.9%) showing life-threatening, polymicrobial, and opportunistic infections constituting a ‘catastrophic infectious syndrome’, which was lethal in 7 cases. Conclusion: IE after treatment by rituximab can be extremely severe, especially in patients immunocompromised by several other drugs. Further studies should focus on the group with life-threatening polymicrobial infections.