Journal Article Epublish
PubMed: 42840466 DOI: 10.1093/ckj/sfag307
Hypophosphatemia after CAR-T cell therapy: a prospective study of inflammation, tubular injury and phosphate handling.
Clin Kidney J 19(10):sfag307
Authors: Francesc Moncho-Francés, Rafael Hernani, Miguel Angel Solis-Salguero, Ana Benzaquén, Isabel Juan-García, Ariadna Pérez-Martínez, Mireia Micó, Juan F Navarro-González, Jose Luis Piñana, Juan Carlos Hernández Boluda, María Jose Terol, Carlos Solano, Jose Luis Górriz, Isidro Torregrosa
Affiliations
- Nephrology Department, Hospital Clínico Universitario de Valencia, INCLIVA Biomedical Research Institute, Valencia, Spain.
- Hematology Department, Hospital Clínico Universitario de Valencia, INCLIVA Biomedical Research Institute, Valencia, Spain.
- Research Unit and Nephrology Department, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain. Institute of Biomedical Technologies, Universidad de La Laguna, La Laguna, Santa Cruz de Tenerife, Spain. Faculty of Health Sciences, Universidad Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain. RICORS2040-RENAL (RD24/0004/0022), Instituto de Salud Carlos III, Madrid, Spain.
- Department of Medicine, Faculty of Medicine, Universitat de València, Valencia, Spain.
- RICORS2040-RENAL (RD24/0004/0022), Instituto de Salud Carlos III, Madrid, Spain.
Abstract
BACKGROUND
Hypophosphatemia is a frequent electrolyte abnormality after chimeric antigen receptor T-cell (CAR-T) therapy, but the clinical and biological factors associated with phosphate decline remain poorly defined. We prospectively evaluated the incidence, determinants, and potential biological associations of hypophosphatemia after CAR-T therapy.
METHODS
We conducted a prospective study including 63 adults with B-cell lymphoma treated with CAR-T therapy between June 2020 and December 2023. Serum phosphate was measured daily during hospitalization. First-morning urine and blood samples were obtained at infusion (D0) and on days +7 (D7) and +14 (D14). Fractional excretion of phosphate (FEPO₄), urine protein-to-creatinine ratio (uPCR), parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23) were assessed. Patients were stratified according to the presence of moderate hypophosphatemia.
RESULTS
Hypophosphatemia occurred in 49/63 patients (78%), including 26 (41%) with moderate hypophosphatemia. Median time to phosphate nadir was 6 days. Patients with moderate hypophosphatemia had higher baseline lactate dehydrogenase levels and Endothelial Activation and Stress Index scores, lower phosphate and creatinine levels at infusion, and a higher frequency of prior ifosfamide exposure. Higher uPCR at D7, higher peak interleukin-6 levels and higher FEPO₄ at D7 were associated with lower phosphate nadir values (ρ = -0.55, P < .001; ρ = -0.55, P < .001; and ρ = -0.31, P = .018, respectively). FGF23 levels were not associated with hypophosphatemia in the primary analysis, while PTH showed a modest inverse association with phosphate nadir in exploratory analysis. Moderate hypophosphatemia was associated with inferior overall survival in univariable analysis.
CONCLUSIONS
Hypophosphatemia is common after CAR-T therapy and was associated with systemic inflammation, urinary markers compatible with partial proximal tubular dysfunction and altered renal phosphate handling. Secondary hyperparathyroidism may have contributed in a subset of patients, whereas FGF23 did not appear to be a dominant explanatory pathway in this cohort.
MeSH
Cells, Creatinine, Hypophosphatemia, Therapeutics, T-Lymphocytes, Prospective Studies, Receptors, Antigen, T-Cell, Car-T Cell