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

Pediatr Nephrol. 2024 Aug;39(8):2495-2503. doi: 10.1007/s00467-024-06331-7. Epub 2024 Mar 20.

Abstract

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.

Keywords: Acute kidney injury; CAR T-cell therapy; CD19-CAR; Pediatric.

MeSH terms

  • Acute Kidney Injury* / epidemiology
  • Acute Kidney Injury* / etiology
  • Acute Kidney Injury* / immunology
  • Acute Kidney Injury* / therapy
  • Adolescent
  • Adult
  • Antigens, CD19* / immunology
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Immunotherapy, Adoptive* / methods
  • Incidence
  • Male
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / complications
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Chimeric Antigen / immunology
  • Retrospective Studies
  • Risk Factors
  • Young Adult

Substances

  • Antigens, CD19
  • CD19-specific chimeric antigen receptor
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen