Characterizing renal complications in immune effector cell therapies in pediatric hematological and solid tumors

Background: Immune effector cell (IEC) therapies including chimeric antigen receptor (CAR)-modified T-cell therapy have shown efficacy in pediatric B-cell acute lymphoblastic leukemia (B-ALL) and are being investigated for other malignancies. A common toxicity associated with IEC therapy is cytokine release syndrome (CRS), which can lead to organ dysfunction due to systemic inflammation causing capillary vasodilation and hypoperfusion. Data is limited regarding acute and chronic renal toxicities in children receiving these therapies. This study describes our institutional experience with renal adverse effects after IEC therapy in pediatric patients. Methods: We retrospectively review patients who received IECs directed toward various antigens in patients with hematologic, solid, and central nervous system malignancies, from January 2014 to June 2023 at Texas Children’s Hospital. The primary endpoint was defined as major adverse kidney events within 90 days acute kidney injury (MAKE90). Results: Two hundred and three patients with a median age of 13 years and 57% male met inclusion criteria. Any grade AKI occurred in 28 patients, all of whom had concurrent CRS. Four patients had AKI-D, two of whom died of disease progression and two of whom recovered. Patients with history of pre-existing renal disease ( p = 0.023) with hematologic malignancy ( p = 0.025) or who received CART products ( p = 0.05) were more likely to have AKI. Most patients had recovery to their pretreatment baseline, with only one patient progressing to new diagnosis of CKD and none needing dialysis at 90-day follow-up. One patient developed biopsy confirmed collapsing variant focal segmental glomerulosclerosis (FSGS) after infusion of CD19 CART product. Conclusions: Significant compromise of renal function including AKI or dialysis occurred in a minority of patients treated with IEC therapy, with most having recovery of renal function within 90 days.