ESPN 53rd Annual Meeting

ESPN 2021


 
Effect of chimeric antigen receptor (CAR) T cell therapy on renal function of pediatric patients: preliminary results
ANDREA CAPPOLI 1 FRANCESCA DEL BUFALO 2 ISABELLA GUZZO 1 FRANCO LOCATELLI 2 MARINA VIVARELLI 1

1- DIVISION OF NEPHROLOGY AND DIALYSIS, DEPARTMENT OF PEDIATRIC SUBSPECIALTIES, IRCCS BAMBINO GESù PEDIATRIC HOSPITAL, ROME ITALY
2- DEPARTMENT OF PEDIATRIC HEMATO-ONCOLOGY AND CELL AND GENE THERAPY, IRCCS BAMBINO GESù PEDIATRIC HOSPITAL, ROME ITALY
 
Introduction:

Cancer immunotherapies are rapidly emerging in pediatric oncology as revolutionary approaches. However, their use may entail unique and severe toxicities that require expert management. Specifically, after chimeric antigen receptor (CAR) T-cell therapy, cytokine release syndrome (CRS) can occur in 30%-80% of patients and lead to acute kidney injury (AKI), owing to direct inflammatory injury, capillary leak syndrome, hypoperfusion and shock.

Material and methods:

We analyzed the effect of CAR T-cell treatment on renal function in 22 children affected by neuroblastoma and treated at the Pediatric Oncology Department of our Hospital, at day 0, +3, +7, +10, +14, +21 and +28 post-infusion. Creatinine clearance (ClCr) was estimated using the Schwartz modified formula for children and the Cockroft-Gault formula for two patients who had just turned 18-year old. Blood pressure, fever and CRS signs and symptoms were recorded. All patients received the same lymphodepletion based on the combination of low-dose Cyclophosphamide and Fludarabine

Results:

At baseline, 3/22 patients had ClCr between 60-90 ml/min/1.73 m2, while 19/22 had >90 ml/min/1.73 m2. In the 28 days following CAR T-cell treatment, we observed no change in renal function in 15/22 patients. The three children with a baseline reduction had an improvement at day +28. In detail, two patients had ClCr >90 ml/min/1.73 m2, while one child increased from 53 to 70 ml/min/1.73 m2. In the remaining four, we observed a transient reduction of ClCr. However, they all completely recovered by day 28. CRS was observed in 16/22 patients (72%) and severe CRS (grade 3 and 4), which required use of inotropes, in two of them (12.5%). All patients who developed AKI presented CRS, but AKI did not correlate with CRS severity.

Conclusions:

Following CAR T-cell therapy, cytokine release syndrome is frequently observed. However, with appropriate management, AKI can be avoided in the vast majority of children.