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Cardiovascular Risks of Tisagenlecleucel in Pediatric Patients: New FAERS Analysis Reveals Critical Safety Signals

• Analysis of FDA Adverse Event Reporting System reveals that nearly one-third (32.92%) of pediatric patients receiving tisagenlecleucel CAR T-cell therapy experienced cardiovascular adverse events, with hypotension being the most common complication.

• Most cardiovascular complications occurred within the first week of treatment and showed significant overlap with cytokine release syndrome, with 90.87% of cardiac events accompanied by CRS.

• Younger age and concurrent use of respiratory medications were associated with increased risk of fatal cardiovascular events, highlighting the need for enhanced monitoring in these patient populations.

A comprehensive analysis of the FDA Adverse Event Reporting System (FAERS) database has revealed significant cardiovascular safety concerns associated with tisagenlecleucel therapy in pediatric patients, providing crucial insights for clinical management of this groundbreaking CAR T-cell treatment.
The study examined data from 568 pediatric patients under 18 years who received tisagenlecleucel, finding that 187 (32.92%) experienced cardiovascular adverse events (CVAEs). Among these cases, 57 resulted in fatalities, representing a 30.48% mortality rate among those with cardiac complications.
Hypotension emerged as the most prevalent cardiovascular complication, with a reporting odds ratio of 30.06 (95% CI 24.65–36.64), followed by tachycardia (ROR 58, 95% CI 9.95–17.22) and hypertension (ROR 4.01, 95% CI 2.35–6.82). The study also documented cases of cardiorespiratory arrest and cardiac arrest.

Timing and Risk Factors

The analysis revealed that cardiovascular complications typically manifested earlier than other adverse events, with a median onset of 3 days post-treatment compared to 7 days for non-cardiovascular complications. Fatal CVAEs occurred even sooner, with a median onset of 2 days compared to 4 days for non-fatal cardiac events.
A striking finding was the substantial overlap between cardiovascular complications and cytokine release syndrome (CRS), with 90.87% of cardiac events accompanied by CRS. This association suggests a potential mechanistic link between these complications.

High-Risk Patient Populations

The study identified several risk factors for adverse cardiovascular outcomes:
  • Patients receiving concurrent medications for neurological conditions showed increased susceptibility to CVAEs
  • Those on respiratory medications demonstrated higher risk for fatal cardiovascular complications
  • Younger patients faced greater risk of fatal outcomes, with the protective effect of age increasing in older pediatric patients

Clinical Implications

These findings underscore the critical importance of enhanced cardiovascular monitoring during the first week following tisagenlecleucel administration, particularly in younger patients and those with concurrent medical conditions. The shorter time to onset for fatal events (2 days) compared to non-fatal complications (4 days) suggests that early intervention could potentially improve outcomes.

Geographic Distribution and Reporting Sources

The majority of cases (76.41%) were reported from the United States, followed by Japan (3.87%), Canada (3.51%), and Spain (2.99%). Medical professionals, particularly physicians (54.58%) and pharmacists (24.12%), submitted most reports, lending credibility to the clinical observations.

Safety Monitoring Recommendations

Given these findings, healthcare providers should implement rigorous cardiovascular monitoring protocols, especially during the first week post-treatment. Particular attention should be paid to:
  • Blood pressure monitoring
  • Cardiac rhythm assessment
  • Early recognition of CRS symptoms
  • Prompt intervention for cardiovascular complications
The study's findings are particularly significant as tisagenlecleucel remains the only CAR T-cell therapy approved for pediatric use, making this safety data crucial for clinical decision-making and risk management strategies.
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