Infection-Related Adverse Events of Tisagenlecleucel in Pediatric Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia: A FAERS Pharmacovigilance Study.

Background

Tisagenlecleucel (tis-cel) is the sole chimeric antigen receptor T-cell (CAR-T) therapy approved for pediatric/adolescent relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). Infection-related adverse events (IRAEs) represent a leading cause of non-relapse mortality, yet dedicated analysis in patients <18 years remains limited.

Objective

This study aimed to analyze the characteristics of IRAEs in pediatric and adolescent patients with r/r B-ALL treated with tis-cel, based on the FDA Adverse Event Reporting System (FAERS) database. The analysis included the reporting proportion, temporal distribution, pathogen spectrum, and overlapping features with other adverse events, generate hypotheses for infection prevention and control in patients aged <18 years. Research Design and

Methods

We analyzed FAERS data (August 2017-March 2025) and included 492 cases of <18-year-old r/r B-ALL patients treated with tis-cel. Disproportionality analyses (reporting odds ratio, ROR; information component, IC), time-to-onset analysis, and co-occurrence assessments were performed on 149 infection-related reports.

Results

Infection-related AEs occurred in 30.28% of cases, with significantly higher mortality in infected versus non-infected patients (40.27% vs. 12.83%, p < 0.001). Most infections (93.86%) occurred within one month (median time-to-onset = 4 days), peaking within 15 days (77.50%); 2.65% occurred after one year. Significant disproportionate reporting signals were observed for Clostridioides difficile (ROR025 = 5.45), influenza virus (ROR025 = 7.16), and adenovirus (ROR025 = 3.51). Hypogammaglobulinemia (52.94%) and hypoxia (54.90%) exhibited higher co-occurrence with infections than CAR-T-specific toxicities (23.08-35.41%).

Conclusions

Infection-related AEs following tis-cel treatment are frequent and associated with significantly increased mortality in pediatric and adolescent r/r B-ALL patients. While most occur early, late infections warrant long-term vigilance. Disproportionality analyses identified signals suggestive of potential high-risk pathogens such as Clostridioides difficile,, influenza, and adenovirus, and hypogammaglobulinemia/hypoxia may serve as early warning indicators. These hypothesis-generating findings require validation in prospective studies.