Abstract：
Chimeric antigen receptor (CAR) T cells are an established treatment for B cell non-Hodgkin lymphomas (B-NHL). With the remarkable success in improving survival, understanding the late effects of CAR T cell therapy is becoming more relevant. The aim of this study is to determine the incidence of subsequent malignancies in adult patients with B-NHL. We retrospectively studied 355 patients from 2 different medical centers treated with four different CAR T cell products from 2016 to 2022. The overall cumulative incidence for subsequent malignancies at 36 months was 14% (95% CI: 9.2%, 19%). Subsequent malignancies were grouped into 3 primary categories: solid tumor, hematologic malignancy, and dermatologic malignancy with cumulative incidences at 36 months of 6.1% (95% CI: 3.1%-10%), 4.5% (95% CI: 2.1%-8.1%) and 4.2% (95% CI: 2.1%-7.5%) respectively. Notably, no cases of T cell malignancies were observed. In univariable analysis, increasing age was associated with higher risk for subsequent malignancy. While the overall benefits of CAR T products continue to outweigh their potential risks, more studies and longer follow ups are needed to further demonstrate the risks, patterns, and molecular pathways that lead to the development of subsequent malignancies.
摘要：
嵌合抗原受体（CAR）T细胞是B细胞非霍奇金淋巴瘤（B-NHL）的既定治疗方法。在提高生存率方面取得了显著成功，了解CAR-T细胞疗法的后期效果变得越来越重要。这项研究的目的是确定成人B-NHL患者随后的恶性肿瘤的发生率。我们回顾性研究了2016年至2022年来自两个不同医疗中心的355名患者，这些患者接受了四种不同的CART细胞产品治疗。36个月后恶性肿瘤的总累积发生率为14%(95%CI:9.2%,19%）。随后的恶性肿瘤分为三个主要类别：实体瘤，恶性血液病,36个月时的累积发病率为6.1%（95%CI：3.1%-10%），4.5%(95%CI:2.1%-8.1%)和4.2%(95%CI:2.1%-7.5%)。值得注意的是,未观察到T细胞恶性肿瘤病例。在单变量分析中，年龄增长与随后发生恶性肿瘤的风险增加相关.虽然CART产品的整体利益继续超过其潜在风险，需要更多的研究和更长时间的随访来进一步证明风险，模式,和导致随后恶性肿瘤发展的分子途径。
