CAR-T 细胞治疗中第二原发恶性肿瘤与抗生素相互作用的药物警戒分析

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.

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.

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.

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.

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. Understanding the association between antibiotics and new cancers in patients receiving CAR-T cell therapy CAR-T therapy has proven to be highly effective in treating certain blood cancers. However, there are concerns about its long-term safety, particularly the risk of secondary primary malignancies (SPMs) new cancers that develop after treatment for the original cancer. This study examines the association between antibiotics, commonly prescribed to CAR-T patients, and the occurrence and timing of these new cancers, using data from the FAERS database. We analyzed reports from April 2017 to March 2024, focusing on SPMs linked to different CAR-T treatments. Our findings suggest that antibiotics are associated with differences in the risk of SPMs depending on the type of CAR-T treatment. Specifically, a lower risk of SPMs was observed in association with antibiotics in patients receiving anti-CD19 CAR-T therapies, like brexucabtagene autoleucel, while a higher risk was observed in those treated with anti-BCMA therapies, particularly idecabtagene vicleucel. Furthermore, antibiotics were linked to an earlier onset of SPMs, suggesting they might accelerate the development of these new cancers. Overall, this highlights the importance of personalized monitoring strategies for CAR-T patients and indicates a need for further research to understand these complex interactions.