Renal and urinary adverse events following CAR-t therapy: A faers-based pharmacovigilance analysis Free

Background: CAR-T therapy is a transformative treatment for relapsed hematologic malignancies and is being explored for autoimmune diseases such as lupus nephritis. CAR-T is associated with significant toxicity, primarily cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). It is also known to be associated with acute kidney injury (AKI), largely in the setting of high-grade CRS, however other potential renal and urinary adverse events (RUAEs) are less well studied. To date, no comprehensive analysis of the FDA Adverse Events Reporting System Database (FAERS) has evaluated CAR-T–associated RUAEs across product classes. This study aims to characterize the incidence and profile of RUAEs to inform safer CAR-T use in both hematologic and rheumatologic diseases.

Methods: We extracted all reports in FAERS between January 2017 and March 2025 and analyzed patients who were treated with FDA approved CAR-T products consisting of5 anti-CD19 CAR-T products (Kymriah, Yescarta, Tecartus, Breyanz, Aucatyzl) and 2 anti-BCMA CAR-T CAR-T products (Abecma, Carvykti). Analysis was performed in R using the Bioconductor package “faers”.Data was standardized using preferred term (PT) according to the FDA's Medical Dictionary for Regulatory Activities (MedDRA). Deduplication was performed based on if reports exhibited full concordance across drugs administered and adverse reactions, but showed discrepancies in one or none of the following fields: gender, age, reporting country, event date, start date, and drug indications. Disproportionality Analysis was performed using reporting odds ratio (ROR).

Results: 11.6 million total reports were extracted. 17,542 reports were related to CAR-T and 872 CAR-T-reports were renal and urinary adverse events per MedDRA classification. RUAEs with 2 or more reports were included for final analysis. Aucatyzl (Obecabtagene Autoleucel) was excluded from analysis as no renal adverse events have been reported thus far. CAR-T were analyzed as a whole, grouped by target (BCMA vs CD19), and individually analyzed by product. 10 RUAEs were significantly overreported overall. AKI was the most common (n=314, 36%, ROR =1.81) and was significantly overreported in both BCMA and CD19 CAR-T (ROR=1.58, ROR=1.85). CD19 CAR-T had 12 significantly overreported RUAE and BCMA had only 1 (AKI). Carvykti (ciltacabtagene autoleucel) was unique in that no RUAE were significantly overreported. Notably, hemorrhagic cystitis, possibly related to cyclophosphamide used as lymphodepleting chemotherapy, was significantly overreported in 16 patients (ROR=5.01). Other newly identified significant RUAE were incontinence (n=60,ROR=7.76), renal tubular necrosis (n=29, ROR=3.88), oliguria (n=18, ROR=4.25), toxic nephropathy (n=17, ROR=1.84), anuria (n=13, ROR=2.27), azotemia (n=12, ROR=4.86), hydronephrosis (n=12, ROR=2.18), and postrenal failure (n=2, ROR=6.82).

Conclusion: We identified a comprehensive list of adverse renal and urinary reactions after CAR-T reported in FAERS. RUAEs are a clinically significant but underrecognized complication of CAR-T therapy. CD19-targeted products were associated with a broader range of renal toxicities than BCMA CAR-Ts. Our data confirm AKI is a common side effect of CAR-T, accounting for around 36% of reported RUAEs, but also showed additional rare adverse events. These findings support close renal monitoring in CAR-T recipients, especially those receiving cyclophosphamide. In addition, consideration of Mesna and preemptive hydration strategies may reduce nephrotoxicity and AKI risk in patients receiving CAR-T therapy.