Department of Pharmacy, Hokkaido University Hospital, Sapporo, Japan.
Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
In Vivo. 2024 Nov-Dec;38(6):2886-2896. doi: 10.21873/invivo.13770.
BACKGROUND/AIM: Immune-related adverse events (irAEs) occur in various organs, and sometimes multiply following treatment with immune checkpoint inhibitors (ICIs). This study aimed to determine the association between the number of irAEs and clinical outcomes.
This was a retrospective study that included patients with lung cancer, melanoma, and head and neck cancer who were treated with anti-programmed cell death (ligand) 1 (PD-1/PD-L1) monotherapy. We evaluated the association between the number of irAEs and progression-free survival (PFS) in the simple Cox regression analysis. To eliminate the immortal-time bias, an additional landmark analysis was performed.
In total, 92, 69, and 37 patients were allocated to the no, single, and multisystem irAEs groups, respectively. The multisystem irAEs were associated with better PFS compared to the no irAE group. In contrast, at the 12-week landmark, multisystem irAEs were associated with poor PFS compared to the no irAEs group. Furthermore, the rate of treatment suspension owing to irAEs in the multisystem irAEs group (62.5%) was higher than that in the single irAE group (17.3%) at the 12-week landmark.
The incidence of multisystem irAEs was associated with improved clinical outcomes in patients with lung cancer, melanoma, and head and neck cancer treated with PD-1/PD-L1 inhibitor monotherapy. However, these results may be influenced by a potential immortal-time bias. When accounting for this bias, the early development of multisystem irAEs within 12 weeks was linked to treatment suspension and poorer clinical outcomes.
背景/目的：免疫相关不良事件（irAEs）发生于各种器官，且在接受免疫检查点抑制剂（ICIs）治疗后有时会多重出现。本研究旨在确定 irAE 的数量与临床结局之间的关联。
这是一项回顾性研究，纳入了接受抗程序性细胞死亡（配体）1（PD-1/PD-L1）单药治疗的肺癌、黑色素瘤和头颈部癌症患者。我们在简单 Cox 回归分析中评估了 irAE 的数量与无进展生存期（PFS）之间的关联。为了消除 Immortal-Time 偏倚，进行了额外的 landmark 分析。
总共将 92、69 和 37 例患者分配至无 irAE、单系统 irAE 和多系统 irAE 组。与无 irAE 组相比，多系统 irAE 与更好的 PFS 相关。相反，在 12 周 landmark 时，与无 irAE 组相比，多系统 irAE 与较差的 PFS 相关。此外，在 12 周 landmark 时，多系统 irAE 组因 irAE 而暂停治疗的比例（62.5%）高于单系统 irAE 组（17.3%）。
在接受 PD-1/PD-L1 抑制剂单药治疗的肺癌、黑色素瘤和头颈部癌症患者中，多系统 irAE 的发生率与改善的临床结局相关。然而，这些结果可能受到潜在 Immortal-Time 偏倚的影响。在考虑到这种偏倚后，在 12 周内发生多系统 irAE 与治疗暂停和较差的临床结局相关。
