Division of Hematologic Malignancies and Cellular Therapeutics, The University of Kansas Cancer Center, Westwood, KS.
Abramson Cancer Center and Center for Cell Therapy and Transplant, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA.
Blood Adv. 2024 Oct 22;8(20):5346-5354. doi: 10.1182/bloodadvances.2023012549.
CD19-directed chimeric antigen receptor T-cell (CAR T) therapies, including axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel), have transformed the treatment landscape for B-cell non-Hodgkin lymphoma, showcasing significant efficacy but also highlighting toxicity risks such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The US Food and Drug Administration has mandated patients remain close to the treatment center for 4 weeks as part of a Risk Evaluation and Mitigation Strategy to monitor and manage these toxicities, which, although cautious, may add to cost of care, be burdensome for patients and their families, and present challenges related to patient access and socioeconomic disparities. This retrospective study across 9 centers involving 475 patients infused with axi-cel, tisa-cel, and liso-cel from 2018 to 2023 aimed to assess CRS and ICANS onset and duration, as well as causes of nonrelapse mortality (NRM) in real-world CAR T recipients. Although differences were noted in the incidence and duration of CRS and ICANS between CAR T products, new-onset CRS and ICANS are exceedingly rare after 2 weeks after infusion (0% and 0.7% of patients, respectively). No new cases of CRS occurred after 2 weeks and a single case of new-onset ICANS occurred in the third week after infusion. NRM is driven by ICANS in the early follow-up period (1.1% until day 28) and then by infection through 3 months after infusion (1.2%). This study provides valuable insights into optimizing CAR T therapy monitoring, and our findings may provide a framework to reduce physical and financial constraints for patients.
CD19 导向嵌合抗原受体 T 细胞(CAR T)疗法,包括 axicabtagene ciloleucel(axi-cel)、tisagenlecleucel(tisa-cel)和 lisocabtagene maraleucel(liso-cel),已经改变了 B 细胞非霍奇金淋巴瘤的治疗格局,展示了显著的疗效,但也凸显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)等毒性风险。美国食品和药物管理局要求患者在 4 周内留在治疗中心附近,作为风险评估和缓解策略的一部分,以监测和管理这些毒性,尽管谨慎,但可能会增加护理成本,给患者及其家人带来负担,并带来与患者获得和社会经济差异相关的挑战。这项回顾性研究在 2018 年至 2023 年期间在 9 个中心进行,涉及 475 名接受 axi-cel、tisa-cel 和 liso-cel 输注的患者,旨在评估 CRS 和 ICANS 的发病和持续时间,以及 CAR T 受体患者非复发死亡率(NRM)的原因。尽管不同的 CAR T 产品在 CRS 和 ICANS 的发生率和持续时间上存在差异,但输注后 2 周后,新发 CRS 和 ICANS 极为罕见(分别为 0%和 0.7%的患者)。输注后 2 周后未发生新的 CRS 病例,在输注后第 3 周发生 1 例新发病例的 ICANS。NRM 在早期随访期间由 ICANS 驱动(28 天内为 1.1%),然后在输注后 3 个月内由感染驱动(1.2%)。这项研究为优化 CAR T 治疗监测提供了有价值的见解,我们的发现可能为减轻患者的身体和经济限制提供了框架。