Pharmacovigilance analysis of secondary primary malignancies and antibiotic interactions in CAR-T cell therapies.

Background: Chimeric antigen receptor T-cell (CAR-T) cell therapy represents a significant advancement in cancer treatment, offering remarkable responses in certain hematologic malignancies. However, the risk of secondary primary malignancies (SPMs) associated with CAR-T therapy is a growing concern. Recent studies suggest that antibiotics, which are frequently used in CAR-T patients, may influence this risk, yet their effects remain poorly understood.

Objective: This study aims to systematically evaluate the association between antibiotics and the incidence and timing of SPMs in patients receiving CAR-T cell therapy, using data from the FDA's Adverse Event Reporting System (FAERS) database.

Design: We analyzed reports from FAERS spanning from Q2 2017 to Q1 2024, focusing on SPMs associated with various CAR-T therapies.

Methods: A comprehensive signal analysis was conducted to explore the associations between antibiotic usage and specific SPMs for different CAR-T products. In addition, we employed cumulative hazard curves to evaluate the time to onset of SPMs in patients receiving antibiotics versus those who did not.

Results: We have provided a comprehensive summary of all signals for CAR-T-associated SPMs. In addition, our analysis identified significant variations in the association between antibiotics and SPM incidence depending on the CAR-T therapy administered. Antibiotics were associated with a decreased risk of SPMs in patients treated with anti-CD19 CAR-T therapies, particularly brexucabtagene autoleucel. Conversely, a higher risk of SPMs was observed in association with antibiotics for anti-BCMA therapies, with idecabtagene vicleucel showing a notably elevated risk. Notably, antibiotics were associated with an earlier onset of SPMs across CAR-T therapies, suggesting a possible relationship between antibiotics and the timing of these malignancies. Finally, we explored the underlying biological pathways that may be associated with these observations.

Conclusion: Antibiotics were associated with both the risk and timing of SPMs in patients undergoing CAR-T cell therapy. This study highlights the need for further research to better understand the complex interactions between antibiotics and CAR-T therapies, as well as the potential implications for clinical management and patient care.