(803) Cardiotoxicity of Immune Effector Cellular Therapies in Pediatric Hematologic and Solid Tumors

Introduction: Immune effector cell (IEC) therapies including chimeric antigen receptor (CAR)-modified T-cell therapy have shown remarkable efficacy in relapsed/refractory pediatric B-acute lymphoblastic leukemia (B-ALL) and are being investigated for other hematological and solid malignancies. The main toxicity is cytokine release syndrome (CRS), which can lead to cardiovascular decompensation. Data are limited regarding the cardiovascular effects of IEC therapies in children, particularly in non-B-ALL malignancies.

Methods: We retrospectively reviewed all patients who received modified immune effector cells directed towards various targets (CD19, GD2, CD5, CD7, CD30, HER2, and EBV or multi-tumor associated (TAA) antigen cytotoxic lymphocytes) from January 2014 to January 2023 at Texas Children’s Hospital. One hundred sixty-five patients were identified, and 163 met inclusion criteria. The primary end point was hypotension requiring vasoactive support and/or heart failure within 30 days of infusion. CRS was graded by the criteria assigned by each protocol. P-values of < 0.05 were considered statistically significant.

Results: Pre-treatment echocardiogram was available for 126 (77%) patients, of whom 122 (97%) had normal baseline systolic function. Hypotension requiring vasoactive support occurred in 25 (15%) patients. Hematologic malignancies (p=0.006), previous exposure to total body irradiation (TBI) (p=0.007), and history of allogenic stem cell transplants (aSCT) (p=0.006) were associated with significantly increased risk of hypotension requiring vasopressors. Eleven patients had echocardiograms during CRS and 3 had depressed ejection fraction greater than 5% from baseline. Five patients had new EKG abnormalities. There were no cardiovascular-related deaths and no patients required ECMO. Follow-up echocardiograms within 6 months were available for 13 of the 25 patients who met the primary endpoint, and all showed return to pre-CRS baseline.

Conclusions: Cardiovascular complications after IEC therapy were observed in 15% of pediatric patients and was more common with hematologic malignancies, TBI, and allogenic SCT. There was no cardiovascular system-related mortality. All patients with cardiovascular compromise during CRS fully recovered cardiac systolic function to baseline within 6 months.