Importance: Rituximab is among the most frequently used immunotherapies in pediatrics. Few studies have reported long-term adverse events associated with its use for children. Objective: To describe the use of rituximab and to assess whether its use is associated with short- or long-term adverse events, infections, or time to immune reconstitution in a diverse group of young people. Design, Setting, and Participants: This retrospective cohort study included 468 patients aged younger than 21 years who received rituximab for diverse indications between October 1, 2010, and December 31, 2017, at Texas Children's Hospital, a large pediatric referral hospital. Patterns of adverse events, infections, and immune recovery are described. Data analyses were conducted from December 2019 to June 2020. Exposure: One or more doses of rituximab. Main Outcomes and Measures: Adverse drug events (eg, anaphylaxis), incidence of mild and severe infections, and time to recovery of B lymphocyte subset counts and immunoglobulin levels. Survival models and logistic regression analyses and were used to identify associated risk factors of infectious and noninfectious adverse drug events. Results: We identified 468 patients receiving at least 1 dose of rituximab. The total follow-up time was 11 713 person-months. Of the 468 patients, 293 (62.6%) were female, the median (interquartile range) age at receipt of dose was 14.3 (9.9-16.8) years, and 209 (44.7%) were self-reported White Hispanic. Adverse events associated with rituximab infusion occurred in 72 patients (15.4%), and anaphylaxis occurred in 17 patients (3.6%). Long-term adverse events, such as prolonged neutropenia and leukoencephalopathy, were absent. Infections occurred in 224 patients (47.9%); 84 patients (17.9%) had severe infections, and 3 patients (0.6%) had lethal infections. Concurrent use of intravenous chemotherapy, treatment of systemic lupus erythematosus, neutropenia, and use of intravenous immunoglobulin were associated with increased risk of infection. Among 135 patients (28.8%) followed up to B cell count recovery, CD19+ or CD20+ cell numbers normalized in a median of 9.0 months (interquartile range, 5.9-14.4 months) following rituximab use; 48 of 95 patients (51%) evaluated beyond a year had low-for-age B cell counts. Recovery of CD27+ memory B cell number occurred in a median of 15.7 months (interquartile range, 6.0-22.7 months). Among patients with normal baseline values, low immunoglobulin G (IgG) levels developed in 67 of 289 patients (23.2%) and low IgM levels in 118 of 255 patients (40.8%); of these patients evaluated beyond 12 months from rituximab, 16 of 117 (13.7%) had persistently low IgG and 37 (33.9%) of 109 had persistently low IgM. Conclusions and Relevance: Rituximab is well tolerated among young people and is associated with few serious adverse events, but infections are common, corresponding to a prolonged period of B cell count recovery often lasting for longer than a year. Further examination of strategies to prevent infections following rituximab should be pursued.
Importance: Rituximab is among the most frequently used immunotherapies in pediatrics. Few studies have reported long-term adverse events associated with its use for children. Objective: To describe the use of rituximab and to assess whether its use is associated with short- or long-term adverse events, infections, or time to immune reconstitution in a diverse group of young people. Design, Setting, and Participants: This retrospective cohort study included 468 patients aged younger than 21 years who received rituximab for diverse indications between October 1, 2010, and December 31, 2017, at Texas Children's Hospital, a large pediatric referral hospital. Patterns of adverse events, infections, and immune recovery are described. Data analyses were conducted from December 2019 to June 2020. Exposure: One or more doses of rituximab. Main Outcomes and Measures: Adverse drug events (eg, anaphylaxis), incidence of mild and severe infections, and time to recovery of B lymphocyte subset counts and immunoglobulin levels. Survival models and logistic regression analyses and were used to identify associated risk factors of infectious and noninfectious adverse drug events. Results: We identified 468 patients receiving at least 1 dose of rituximab. The total follow-up time was 11 713 person-months. Of the 468 patients, 293 (62.6%) were female, the median (interquartile range) age at receipt of dose was 14.3 (9.9-16.8) years, and 209 (44.7%) were self-reported White Hispanic. Adverse events associated with rituximab infusion occurred in 72 patients (15.4%), and anaphylaxis occurred in 17 patients (3.6%). Long-term adverse events, such as prolonged neutropenia and leukoencephalopathy, were absent. Infections occurred in 224 patients (47.9%); 84 patients (17.9%) had severe infections, and 3 patients (0.6%) had lethal infections. Concurrent use of intravenous chemotherapy, treatment of systemic lupus erythematosus, neutropenia, and use of intravenous immunoglobulin were associated with increased risk of infection. Among 135 patients (28.8%) followed up to B cell count recovery, CD19+ or CD20+ cell numbers normalized in a median of 9.0 months (interquartile range, 5.9-14.4 months) following rituximab use; 48 of 95 patients (51%) evaluated beyond a year had low-for-age B cell counts. Recovery of CD27+ memory B cell number occurred in a median of 15.7 months (interquartile range, 6.0-22.7 months). Among patients with normal baseline values, low immunoglobulin G (IgG) levels developed in 67 of 289 patients (23.2%) and low IgM levels in 118 of 255 patients (40.8%); of these patients evaluated beyond 12 months from rituximab, 16 of 117 (13.7%) had persistently low IgG and 37 (33.9%) of 109 had persistently low IgM. Conclusions and Relevance: Rituximab is well tolerated among young people and is associated with few serious adverse events, but infections are common, corresponding to a prolonged period of B cell count recovery often lasting for longer than a year. Further examination of strategies to prevent infections following rituximab should be pursued.
Authors: I Fleury; S Chevret; M Pfreundschuh; G Salles; B Coiffier; M H J van Oers; C Gisselbrecht; E Zucca; M Herold; M Ghielmini; C Thieblemont Journal: Ann Oncol Date: 2015-12-17 Impact factor: 32.976
Authors: Davide Bedognetti; Gabriele Zoppoli; Carlotta Massucco; Elisa Zanardi; Simonetta Zupo; Andrea Bruzzone; Mario Roberto Sertoli; Enrico Balleari; Omar Racchi; Marco Messina; Graziano Caltabiano; Giancarlo Icardi; Paolo Durando; Francesco M Marincola; Francesco Boccardo; Manlio Ferrarini; Filippo Ansaldi; Andrea De Maria Journal: J Immunol Date: 2011-04-15 Impact factor: 5.422
Authors: Russell C Dale; Fabienne Brilot; Lisa V Duffy; Marinka Twilt; Amy T Waldman; Sona Narula; Eyal Muscal; Kumaran Deiva; Erik Andersen; Michael R Eyre; Despina Eleftheriou; Paul A Brogan; Rachel Kneen; Gulay Alper; Banu Anlar; Evangeline Wassmer; Kirsten Heineman; Cheryl Hemingway; Catherine J Riney; Andrew Kornberg; Marc Tardieu; Amber Stocco; Brenda Banwell; Mark P Gorman; Susanne M Benseler; Ming Lim Journal: Neurology Date: 2014-06-11 Impact factor: 9.910
Authors: Brian D Friend; Ibrahim N Muhsen; Shreeya Patel; LaQuisa C Hill; Premal Lulla; Carlos A Ramos; S Ravi Pingali; Rammurti T Kamble; Tami D John; Baheyeldin Salem; Saleh Bhar; Erin E Doherty; John Craddock; Ghadir Sasa; Mengfen Wu; Tao Wang; Caridad Martinez; Robert A Krance; Helen E Heslop; George Carrum Journal: Bone Marrow Transplant Date: 2022-02-01 Impact factor: 5.483
Authors: Natalia Riva; Manuel Molina; Berta L Cornaló; María V Salvador; Andrea Savransky; Silvia Tenembaum; María M Katsicas; Marta Monteverde; Paulo Cáceres Guido; Marcela Rousseau; Raquel Staciuk; Agustín González Correas; Pedro Zubizarreta; Oscar Imventarza; Eduardo Lagomarsino; Eduardo Spitzer; Marcelo Tinelli; Paula Schaiquevich Journal: Front Pharmacol Date: 2022-01-26 Impact factor: 5.810