Infection-Related Adverse Events of Tisagenlecleucel in Pediatric Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia: A FAERS Pharmacovigilance Study.
In a FAERS analysis of 492 reported pediatric tisagenlecleucel-treated r/r B-ALL cases, 149 included infection-related events that clustered early, were associated with higher reported mortality, and generated disproportionate-reporting signals for Clostridioides difficile, influenza virus, and adenovirus.
Open original publication →What the AI sees
In a FAERS analysis of 492 reported pediatric tisagenlecleucel-treated r/r B-ALL cases, 149 included infection-related events that clustered early, were associated with higher reported mortality, and generated disproportionate-reporting signals for Clostridioides difficile, influenza virus, and adenovirus.
Research significance
The record supports hypothesis generation—not clinical validation—that intensified early infection surveillance, longer-term vigilance, and attention to selected pathogens, hypogammaglobulinemia, and hypoxia might help identify high-risk pediatric tisagenlecleucel recipients; whether targeted monitoring or prophylaxis improves outcomes requires prospective testing.
Source abstract
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.