Jean-Jacques Tudesq1, Guillaume Cartron2, Sophie Rivière3, David Morquin4, Laura Iordache5, Alfred Mahr5, Valérie Pourcher6, Kada Klouche7, Diane Cerutti3, Alain Le Quellec3, Philippe Guilpain8. 1. Internal Medicine and Multi-organic Diseases Department, Local Referral Center for Rare Autoimmune Diseases, Montpellier University Hospital, Montpellier F-34000, France; Medical Intensive Care Unit, Montpellier University Hospital, Montpellier F-34000, France. 2. Clinical Hematology Department, Montpellier University Hospital, Montpellier, F-34000, France; Centre National de Recherche Scientifique (CNRS), UMR 5235, Montpellier University, Montpellier F-34000, France. 3. Internal Medicine and Multi-organic Diseases Department, Local Referral Center for Rare Autoimmune Diseases, Montpellier University Hospital, Montpellier F-34000, France. 4. Infectious Diseases Department, Montpellier University Hospital, Montpellier, F-34000, France. 5. Internal Medicine Department, Saint-Louis University Hospital, AP-HP, Paris F-75010, France. 6. Infectious Diseases Department, Pitié-Salpêtrière University Hospital, AP-HP, Paris F-75005, France. 7. Medical Intensive Care Unit, Montpellier University Hospital, Montpellier F-34000, France. 8. Internal Medicine and Multi-organic Diseases Department, Local Referral Center for Rare Autoimmune Diseases, Montpellier University Hospital, Montpellier F-34000, France; Institut National de la Santé Et de la Rercherche Médicale (INSERM) U1183, Institute for Regenerative Medicine and Biotherapies (IRMB), Montpellier F-34000, France. Electronic address: p-guilpain@chu-montpellier.fr.
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 30.4months). 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 4340mg [2620-6160]. After last rituximab infusion, IE occurred after 3.1months [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 10mg/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.
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 30.4months). 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 4340mg [2620-6160]. After last rituximab infusion, IE occurred after 3.1months [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 10mg/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.
Authors: Sylvain Lamure; Jon Salmanton-García; Elena Robin-Marieton; Ozren Jaksic; Milena Kohn; Francesco Marchesi; Monia Marchetti; Shaimaa El-Ashwah; Fatih Demirkan; Toni Valković; Noemí Fernández; Maria Chiara Tisi; Zlate Stojanoski; Guldane Cengiz Seval; Osman Ilhan; Lucia Prezioso; Maria Merelli; Alberto López-García; Marie-Pierre Ledoux; Austin Kulasekararaj; Tomás-José González-López; Maria Gomes da Silva; Ziad Emarah; Rafael F Duarte; Chiara Cattaneo; Ola Blennow; Yavuz M Bilgin; Rui Bergantim; Josip Batinić; Raul Cordoba; Jenna Essame; Anna Nordlander; Raquel Nunes Rodrigues; Maria Vittoria Sacchi; Sofia Zompi; Alessandro Busca; Paolo Corradini; Martin Hoenigl; Nikolai Klimko; Philipp Koehler; Antonio Pagliuca; Francesco Passamonti; Rémy Duléry; Oliver A Cornely; Caroline Besson; Livio Pagano Journal: Blood Adv Date: 2022-07-12