Factors Influencing Early and Late B-Cell Repopulation After Rituximab Therapy in Pediatric Central Nervous System Inflammatory Disorders.

OBJECTIVES

To identify factors associated with early and late B-cell repopulation in pediatric patients with neuroimmune disorders treated with rituximab (RTX), and to provide practical guidance on treatment protocols.

METHODS

This single-center retrospective study included pediatric patients with central nervous system neuroinflammatory disorders treated with RTX from January 2014 to December 2023, and who had at least one CD19+ B-cell test. B-cell depletion was defined as an absolute CD19+ cell count of ≤10 cells/μL after treatment. Early repopulation was defined as >10 cells/μL at 150 days; late repopulation was considered as ≤10 cells/μL after 210 days. Predictors of early and late B-cell repopulation were evaluated using univariate and multivariate generalized linear mixed models. Relapses during B-cell repopulation and adverse events were recorded across all participants.

RESULTS

The study included 152 patients. Early B-cell repopulation was noted in 32 patients and was associated with younger age at first infusion (odds ratio [OR] = 0.2, 95% confidence interval [CI]: 0.1-0.4). Late repopulation in 52 patients was associated to older age at first infusion (OR = 1.09, 95% CI: 1.02-1.16) and higher number of infusions (OR = 1.17, 95% CI: 1.08-1.2). Patients with multiple sclerosis did not experience relapses during repopulation. Patients switched to a single RTX dose remained adequately depleted. Adverse events were reported in 26% of the cohort, with hypogammaglobulinemia being the most common (23/152, 15%).

CONCLUSIONS

Age and the number of infusions influence the timing of B-cell repopulation. Tailoring RTX regimens and ongoing monitoring, considering age, diagnosis, and treatment duration, can optimize RTX benefits while minimizing risks.