Acute kidney injury following treatment with CD19-specific CAR T-cell therapy in children, adolescent, and young adult patients with B-cell acute lymphoblastic leukemia

• Published in: Pediatric nephrology (Berlin, West) Vol. 39; no. 8; pp. 2495 - 2503
• Main Authors: Petgrave, Yonique, Selukar, Subodh, Epperly, Rebecca, Naik, Swati, Santos, Noel DeLos, Triplett, Brandon M., Gottschalk, Stephen, Bissler, John, Talleur, Aimee C.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-08-2024; Springer Nature B.V
• Subjects: Acute lymphoblastic leukemia; CD19 antigen; Cell therapy; Chimeric antigen receptors; Kidneys; Lymphatic leukemia; Lymphocytes B; Lymphocytes T; Malignancy; Medicine; Medicine & Public Health; Nephrology; Neurotoxicity; Original Article; Patients; Pediatrics; Population studies; Renal function; Risk factors; Urology; What’s new in AKI; Young adults; CAR T-cell therapy; CD19-CAR; Pediatric; Acute kidney injury
• ISSN: 0931-041X; 1432-198X; 1432-198X
• DOI: 10.1007/s00467-024-06331-7

Background
CD19-specific chimeric antigen receptor (CAR) T-cell therapy has shown promising disease responses in patients with high-risk B-cell malignancies. However, its use may be related to complications such as immune-mediated complications, infections, and end-organ dysfunction. The incidence of post-CAR T-cell therapy acute kidney injury (AKI) in the children, adolescent, and young adult (CAYA) patient population is largely unreported.
Methods
The objectives of this study were to determine the incidence of AKI in CAYA patients with high-risk B-cell malignancies treated with CD19-CAR T-cell therapy, evaluate potential risk factors for developing AKI, and determine patterns of kidney function recovery. We conducted a retrospective analysis of 34 CAYA patients treated with CD19-CAR T-cell at a single institution.
Results
There was a cumulative incidence of any grade AKI by day 30 post-infusion of 20% (
n
 = 7), with four cases being severe AKI (stages 2–3) and one patient requiring kidney replacement therapy. All episodes of AKI developed within the first 14 days after receiving CAR T-cell therapy and 50% of patients with AKI recovered kidney function to baseline within 30 days post-infusion. No evaluated pre-treatment risk factors were associated with the development of subsequent AKI; there was an association between AKI and cytokine release syndrome and neurotoxicity. We conclude that the risk of developing AKI following CD19-CAR T-cell therapy is highest early post-infusion, with most cases of AKI being severe.
Conclusions
Frequent monitoring to facilitate early recognition and subsequent management of kidney complications after CD19-CAR T-cell therapy may reduce the severity of AKI in the CAYA patient population.
Graphical abstract
A higher resolution version of the Graphical abstract is available as
Supplementary information