Peng Yun, Song Yuxuan, Lin Jiaxing, Qin Caipeng, Du Yiqing, Xu Tao
Department of Urology, Peking University People's Hospital, Beijing, China.
The Institute of Applied Lithotripsy Technology, Peking University, Beijing, China.
Ther Adv Drug Saf. 2025 Jun 5;16:20420986251340866. doi: 10.1177/20420986251340866. eCollection 2025.
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.
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.
嵌合抗原受体T细胞（CAR-T）疗法是癌症治疗领域的一项重大进展，在某些血液系统恶性肿瘤中疗效显著。然而，与CAR-T疗法相关的继发性原发性恶性肿瘤（SPM）风险日益受到关注。近期研究表明，CAR-T患者常用的抗生素可能会影响这一风险，但其影响仍知之甚少。
本研究旨在利用美国食品药品监督管理局不良事件报告系统（FAERS）数据库的数据，系统评估接受CAR-T细胞疗法的患者中抗生素与SPM的发生率及发生时间之间的关联。
我们分析了2017年第二季度至2024年第一季度FAERS的报告，重点关注与各种CAR-T疗法相关的SPM。
进行了全面的信号分析，以探究不同CAR-T产品抗生素使用与特定SPM之间的关联。此外，我们采用累积风险曲线来评估接受抗生素治疗的患者与未接受抗生素治疗的患者发生SPM的时间。
我们全面总结了所有与CAR-T相关的SPM信号。此外，我们的分析发现，根据所施用的CAR-T疗法不同，抗生素与SPM发生率之间的关联存在显著差异。在接受抗CD19 CAR-T疗法（尤其是布雷西尤单抗）治疗的患者中，抗生素与SPM风险降低相关。相反，在抗BCMA疗法中，观察到抗生素与SPM风险较高相关，其中艾代尤单抗风险显著升高。值得注意的是，在所有CAR-T疗法中，抗生素与SPM的发病时间较早相关，这表明抗生素与这些恶性肿瘤的发生时间之间可能存在关联。最后，我们探究了可能与这些观察结果相关的潜在生物学途径。
抗生素与接受CAR-T细胞疗法患者的SPM风险和发生时间均相关。本研究强调需要进一步开展研究，以更好地理解抗生素与CAR-T疗法之间的复杂相互作用，以及对临床管理和患者护理的潜在影响。
