CAR-T Cells and the Kidney: Insights from the WHO Safety Database

Area of Science:

• Pharmacovigilance
• Oncology
• Nephrology

Background:

• Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized hematologic malignancy treatment.
• Adverse drug reactions (ADRs), including cytokine release syndrome (CRS), are known risks.
• Acute renal failure (ARF) affects up to 20% of patients, necessitating further real-world safety analysis.

Purpose of the Study:

• To analyze real-world data on the renal safety of CAR-T cell therapy.
• To investigate the association between CAR-T cells and ARF and hydroelectrolytic disorders.

Main Methods:

• Utilized VigiBase® database for reports of ARF and hydroelectrolytic disorders associated with CAR-T cells until July 2022.
• Employed disproportionality analysis using the Information Component (IC) with a 95% confidence interval (CI) for signal detection.
• Assessed ARF reports, excluding those mentioning CRS, and analyzed various electrolyte disorders.

Main Results:

• Identified 224 reports of ARF and 125 reports of hydroelectrolytic disorders linked to CAR-T cells.
• CAR-T cells showed disproportionate reporting for ARF (IC 1.5 [1.3-1.7]), even excluding CRS cases.
• Significant disproportionality observed for hypernatremia, hyperphosphatemia, hypophosphatemia, metabolic acidosis, hyponatremia, and hypercalcemia.

Conclusions:

• Acute renal failure (ARF) and several hydroelectrolytic disorders are potential adverse drug reactions (ADRs) associated with CAR-T cell therapy.
• Findings are based on real-world data, highlighting risks in a non-selected population.
• Pharmacovigilance limitations are acknowledged, but the signals warrant attention for clinical practice.