Assessing the risk of cytokine release syndrome associated with the use of antineoplastic agents: A real-world pharmacovigilance study based on the FDA Adverse Event Reporting System database (FAERS).

Abstract

e23359 Background: Cytokine Release Syndrome (CRS) is a severe immune-related toxicity commonly observed with immune-modulating therapies, particularly CAR-T cell therapies and bispecific T-cell engagers (BiTEs). Given the increasing use of these agents in oncology, it is crucial to assess their safety profiles. This study aims to analyze the top 10 drugs most frequently associated with CRS in FAERS using disproportionality metrics, including the Relative Reporting Ratio (RRR), Proportional Reporting Ratio (PRR), and Reporting Odds Ratio (ROR). Methods: A disproportionality analysis was conducted using FAERS data to identify the top 10 drugs associated with CRS. The analysis focused on key pharmacovigilance metrics: Relative Reporting Ratio (RRR), Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), Chi-Squared with Yates’ Correction. Drugs were ranked based on ROR values, which provide a measure of association strength between a drug and CRS. Results: Among the top 10 drugs associated with CRS, CAR-T therapies exhibited the strongest disproportionality signals, with Axicabtagene Ciloleucel (ROR: 1946.596, PRR: 1104.019), Tisagenlecleucel (ROR: 1541.613, PRR: 908.159), and Brexucabtagene Autoleucel (ROR: 1385.781, PRR: 815.937) ranking highest. These findings suggest a strong association between CRS and CAR-T therapies, consistent with their well-documented immune-mediated toxicities, including cytokine release syndrome. Blinatumomab (ROR: 216.203, PRR: 195.902), a BiTE therapy, ranked fourth, reflecting a moderate but significant CRS signal. Fludarabine (ROR: 128.879, PRR: 121.137), an immunosuppressive agent used in lymphodepleting regimens before CAR-T therapy, also exhibited a notable CRS association, likely due to its role in enhancing immune cell expansion. Traditional chemotherapy agents demonstrated lower CRS signals, with Cyclophosphamide (ROR: 26.215, PRR: 25.886) and monoclonal antibody Rituximab (ROR: 6.973, PRR: 6.952) showing relatively modest disproportionality. Corticosteroids, which are commonly used to mitigate CRS symptoms, had the lowest disproportionality signals, with Dexamethasone (ROR: 5.752, PRR: 5.738) and Prednisone (ROR: 1.879, PRR: 1.878) exhibiting minimal CRS association. Conclusions: This FAERS-based analysis confirms that CAR-T therapies and BiTEs exhibit the highest association with CRS, emphasizing the need for stringent monitoring and risk mitigation strategies. Traditional chemotherapy agents, though sometimes implicated in CRS, displayed lower signals, while corticosteroids showed the weakest association, consistent with their role in CRS management. These findings reinforce the importance of continued pharmacovigilance efforts to optimize the safety of emerging immunotherapies in oncology.