Predictors and implications of renal injury after CD19 chimeric antigen receptor T-cell therapy

Autor: Alexander P. Boardman, Victoria Gutgarts, Jessica Flynn, Sean M. Devlin, Adam Goldman, Ana Alarcon Tomas, Joshua A. Fein, John B. Slingerland, Allison Parascondola, Richard J. Lin, Michael Scordo, Parastoo B. Dahi, Sergio Giralt, M. Lia Palomba, Gilles Salles, Karthik Nath, Moneeza Walji, Magdalena Corona, Jae H. Park, Gunjan L. Shah, Miguel-Angel Perales, Insara Jaffer-Sathick, Roni Shouval
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Haematologica, Vol 999, Iss 1 (2024)
Druh dokumentu: article
ISSN: 0390-6078
1592-8721
DOI: 10.3324/haematol.2024.286021
Popis: Chimeric Antigen Receptor (CAR) T cells targeting CD19 induce durable remissions in patients with relapsed or refractory non-Hodgkin lymphoma (NHL), but many patients experience treatmentrelated toxicity. Cytokine release syndrome and immune effector cell-associated neurologic syndrome are extensively characterized. However, limited data exist on the burden, predictors, and implications of acute kidney injury (AKI) after CAR T cell therapy. On initial screening of the FDA adverse event reporting system, we identified a disproportionately high rate of renal adverse events among nearly 6,000 CAR T adverse event reports, suggesting it is clinically important in this patient population. In a subsequent single-center analysis of 399 NHL patients treated with CD19 CAR T cells, we found a substantial burden of AKI after CAR T infusion (10% and 5% of any grade and grade ≥2 AKI) with pre-renal causes being predominant (72%). Evolution to chronic kidney disease was rare, however, 3 patients required hemodialysis. Importantly, patients experiencing cytokine release syndrome and/or neurotoxicity as well as those with low serum albumin and high inflammatory cytokines, including IL-6 and TNF-alpha, were more likely to develop AKI. While pre-CAR T renal dysfunction was not associated with adverse outcomes, patients developing post-CAR T AKI had lower overall survival compared to their counterparts. Our findings indicate that renal dysfunction is a common toxicity of CAR T cell therapy with meaningful prognostic impact. Notably, the link between systemic inflammation and renal dysfunction, suggests that readily available biomarkers may inform on renal injury risk after CAR T cell therapy.
Databáze: Directory of Open Access Journals
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