Liu Yang, Yuan Xiaoshuang, Yang Xu, Yang Bo, Liu Guangyang, Xu Xiao, Wang Sanbin, He Zhixu, Wang Feiqing, Li Yanju
Clinical Medical Research Center, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No. 71 Bao Shan North Road, Yunyan District, Guiyang, 550001, Guizhou, China.
Department of Hematology Oncology, Affiliated Hospital of Guizhou Medical University, No. 4 Bei Jing Road, Yunyan District, Guiyang, 550004, Guizhou, China.
J Transl Med. 2025 Jan 4;23(1):8. doi: 10.1186/s12967-024-06035-4.
Anti-CD19 chimeric antigen receptor (CAR) T cell therapy is a common, yet highly efficient, cellular immunotherapy for lymphoma. However, many recent studies have reported on its cardiovascular (CV) toxicity. This study analyzes the cardiotoxicity of CD19 CAR T cell therapy in the treatment of lymphoma for providing a more valuable reference for clinicians.
The PubMed, Embase, Cochrane library, and Web of Science databases were comprehensively searched from the time of their establishment to May 2024. The ClinicalTrials.gov English database is a comprehensive repository of the original studies of CD19 CAR T cell therapy and associated adverse outcomes, such as arrhythmia, CV events, and hypotension, in patients with lymphoma. The Cochrane Collaboration tool and the Newcastle-Ottawa Scale (NOS) were used to assess the quality of the included original studies. For RCTs, the Cochrane Collaboration tool was used to assess the risk of bias. For non-randomized studies, the risk of bias was assessed using the NOS quality assessment scale.
A risk analysis of two randomized controlled trials and nine cohort studies, totaling 1379 patients with lymphoma receiving CD19 CAR-T, is conducted. The incidences for all-cause mortality, CV events, and hypotension were found to be 17.8%, 17.8%, and 52.8%, respectively. Additionally, the incidences of heart failure (HF), cardiomyopathy, cardiac arrest, and other CV events are 3%, 0.6%, 1.3%, and 2.5%, respectively. In addition to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) as adverse events, patients treated with CD19 CAR T cells are also at risk of CV events. The most common CV events are arrhythmia and HF. Our further analysis showed that the incidence of CV events was 28.7% in the elderly and 13.5% in adults. The incidence of CV events in the elderly was higher than that in adults, and it was statistically significant. Furthermore, the incidence of CV events and hypotension is strongly associated with patients with CRS.
Therefore, clinicians should pay close attention to the occurrence of such CV events and take timely prevention and intervention measures to further improve the safety of CD19 CAR T cell therapy.
抗CD19嵌合抗原受体（CAR）T细胞疗法是一种常见但高效的淋巴瘤细胞免疫疗法。然而，最近许多研究都报道了其心血管（CV）毒性。本研究分析CD19 CAR T细胞疗法在治疗淋巴瘤中的心脏毒性，以便为临床医生提供更有价值的参考。
全面检索了PubMed、Embase、Cochrane图书馆和Web of Science数据库，检索时间从建库至2024年5月。ClinicalTrials.gov英文数据库全面收录了CD19 CAR T细胞疗法及淋巴瘤患者相关不良结局（如心律失常、CV事件和低血压）的原始研究。采用Cochrane协作工具和纽卡斯尔-渥太华量表（NOS）评估纳入的原始研究的质量。对于随机对照试验，使用Cochrane协作工具评估偏倚风险。对于非随机研究，使用NOS质量评估量表评估偏倚风险。
对两项随机对照试验和九项队列研究进行了风险分析，共有1379例接受CD19 CAR-T治疗的淋巴瘤患者。发现全因死亡率、CV事件和低血压的发生率分别为17.8%、17.8%和52.8%。此外，心力衰竭（HF）、心肌病、心脏骤停和其他CV事件的发生率分别为3%、0.6%、1.3%和2.5%。除了细胞因子释放综合征（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）作为不良事件外，接受CD19 CAR T细胞治疗的患者也有发生CV事件的风险。最常见的CV事件是心律失常和HF。我们的进一步分析表明，老年人CV事件的发生率为28.7%，成年人中为13.5%。老年人CV事件的发生率高于成年人，且具有统计学意义。此外，CV事件和低血压的发生率与CRS患者密切相关。
因此，临床医生应密切关注此类CV事件的发生，并及时采取预防和干预措施，以进一步提高CD19 CAR T细胞疗法的安全性。
