Patterns of B Cell Repletion Following Rituximab Therapy in a Pediatric Rheumatology Cohort

Mitchell, Chace; Crayne, Courtney B.; Cron, Randy Q.

doi:10.1002/acr2.11074

Cited by 17 publications

(10 citation statements)

References 26 publications

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“…Evaluation within a month of a dose to confirm lymphodepletion is unnecessary in most cases; of 104 CD20 + evaluations, all had low-for-age values, and only 2 had a value greater than 0 (Figure, B). Similar to other studies, B cell counts in young people evaluated in the present study usually recovered within a year, but recovery was often delayed . Approximately half of the patients evaluated beyond a year had low-for-age B cell counts, suggesting that their prolonged suppression is common in children.…”

Section: Discussionsupporting

confidence: 86%

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Association of Rituximab Use With Adverse Events in Children, Adolescents, and Young Adults

et al. 2021

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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 shortor 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-forage 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.

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Section: Discussionsupporting

confidence: 86%

“…Similar to other studies, B cell counts in young people evaluated in the present study usually recovered within a year, but recovery was often delayed. 2,7,27,43 Approximately half of the patients evaluated beyond a year had low-for-age B cell counts, suggesting that their prolonged suppression is common in children.…”

Section: Discussionmentioning

confidence: 99%

Association of Rituximab Use With Adverse Events in Children, Adolescents, and Young Adults

et al. 2021

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“…In this regard, the COVID-19 pandemic and its higher risk of severe infection observed in some MS patients treated with anti-CD20 MAbs may lead to consideration of an adjusted dose according to individualized monitoring of B cell repopulation [32]. Mean time of B cell repopulation after rituximab usually varies between 6 and 9 months, but with a high interindividual and intraindividual variability [34,35]. However, studies evaluating B cell repopulation after anti-CD20 MAbs are limited, mainly explained by the need to continually administer rituximab in an onco-hematological scenario.…”

Section: Clinical Outcome Of Ms Patients Treated With Rituximabmentioning

confidence: 99%

Delayed B cell repopulation after rituximab treatment in multiple sclerosis patients with expanded adaptive natural killer cells

Moreira

Munteis

Vera

et al. 2022

Euro J of Neurology

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Background and purpose The aim was to evaluate whether adaptive NKG2C+ natural killer (NK) cells, characterized by enhanced antibody‐dependent cell cytotoxicity (ADCC), may influence time to B cell repopulation after rituximab treatment in multiple sclerosis (MS) patients. Methods This was a prospective observational study of MS patients treated with rituximab monitoring peripheral B cells for repeated doses. B cell repopulation was defined as CD19+ cells above 2% of total lymphocytes, classifying cases according to the median time of B cell repopulation as early or late (≤9 months, >9 months, respectively). Basal NK cell immunophenotype and in vitro ADCC responses induced by rituximab were assessed by flow cytometry. Results B cell repopulation in 38 patients (24 relapsing–remitting MS [RRMS]; 14 progressive MS) was classified as early (≤9 months, n = 19) or late (>9 months, n = 19). RRMS patients with late B cell repopulation had higher proportions of NKG2C+ NK cells compared to those with early repopulation (24.7% ± 16.2% vs. 11.3% ± 10.4%, p < 0.05), and a direct correlation between time to B cell repopulation and percentage of NKG2C+ NK cells (R 0.45, p < 0.05) was observed. RRMS cases with late repopulation compared with early repopulation had a higher secretion of tumor necrosis factor α and interferon γ by NK cells after rituximab‐dependent NK cell activation. The NK cell immunophenotype appeared unrelated to B cell repopulation in progressive MS patients. Conclusions Adaptive NKG2C+ NK cells in RRMS may be associated with delayed B cell repopulation after rituximab, a finding probably related to enhanced depletion of B cells exerted by NK‐cell‐mediated ADCC, pointing to the use of personalized regimens with anti‐CD20 monoclonal antibody therapy in some patients.

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“…Peripheral CD19 + B-cell and CD4 + T cell counts were determined by flow cytometry (Navios; Beckman Coulter, Brea, CA, USA). B-cell depletion was defined as a CD19 + count < 10 cells/μL [ 7 ]. CD19 + cells were classified into CD19 + CD5 + and CD19 + CD5 − cells by flow cytometry.…”

Section: Methodsmentioning

confidence: 99%

Efficacy and safety of low-dose rituximab as induction therapy for antineutrophil cytoplasmic antibody-associated vasculitis with renal involvement: a Chinese case series

et al. 2023

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Background Rituximab (RTX) is a standard therapy for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, the most frequently used dose may lead to severe adverse effects (SAEs). We explored the efficacy and safety of low-dose RTX in Chinese patients with AAV. Methods A total of 22 Chinese patients diagnosed with AAV with renal involvement, including 8 treated with low-dose RTX (400 mg of RTX total over 4 weeks) and 14 treated with cyclophosphamide (CYC), were evaluated. The baseline clinical and pathological data and laboratory parameters during follow-up at months 1, 3, 6, and 12 were collected retrospectively. Results The baseline data showed no significant differences between the two groups. The median peripheral CD19+ cell counts in the RTX group decreased from 315.0/μL to 1.5/μL at 2 weeks, and to 2.5/μL at 1 month after the first dose. The median SCr level decreased from 267.8 μmol/L before treatment to 151.45 μmol/L at 1 month, 132.75 μmol/L at 3 months, 123.2 μmol/L at 6 months, and 151.9 μmol/L at 12 months in RTX-treated patients. The improvements in renal function, proteinuria, and ANCA titre were not significantly different between the two groups. The SAE rate was significantly lower in the RTX group (one SAE of pneumonia) compared with the CYC group. Conclusions This is the first report that low-dose RTX could be effective for the treatment of Chinese patients with AAV with renal involvement.

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Patterns of B Cell Repletion Following Rituximab Therapy in a Pediatric Rheumatology Cohort

Cited by 17 publications

References 26 publications

Association of Rituximab Use With Adverse Events in Children, Adolescents, and Young Adults

Association of Rituximab Use With Adverse Events in Children, Adolescents, and Young Adults

Delayed B cell repopulation after rituximab treatment in multiple sclerosis patients with expanded adaptive natural killer cells

Efficacy and safety of low-dose rituximab as induction therapy for antineutrophil cytoplasmic antibody-associated vasculitis with renal involvement: a Chinese case series

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