Nakazawa Yusuke, Gannichida Ako, Utsumi Hirofumi, Araya Jun, Kawakubo Takashi
Department of Pharmacy, The Jikei University Hospital, Tokyo, JPN.
Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, JPN.
Cureus. 2025 Mar 4;17(3):e80049. doi: 10.7759/cureus.80049. eCollection 2025 Mar.
Introduction Pembrolizumab, an immune checkpoint inhibitor targeting programmed death-1 (PD-1)/PD-1 ligand (PD-L1), has demonstrated antitumor effects but can cause immune-related adverse events (irAEs) such as hypothyroidism. The neutrophil-to-lymphocyte ratio (NLR) may be linked to pembrolizumab efficacy and irAE risk. This study investigated the relationship between NLR trends and hypothyroidism onset, assessing its predictive potential. Methods This retrospective study analyzed 136 patients with advanced or recurrent cancer treated with pembrolizumab at The Jikei University Hospital, Tokyo, Japan, from February 2017 to September 2023. Patients were categorized based on hypothyroidism development, and their baseline NLR and time to treatment failure (TTF) were compared. NLR trends before hypothyroidism onset were also evaluated. Patients were further stratified based on onset timing (<90 days vs. ≥90 days), and NLR parameters prior to onset were also compared. Results Hypothyroidism occurred in 33 of 136 patients (24%). The hypothyroidism group had a significantly lower baseline NLR (P = 0.006) and longer TTF (P = 0.006). No significant NLR changes were observed before hypothyroidism onset (P = 0.626). However, the maximum NLR until onset was significantly lower in patients with early-onset hypothyroidism (<90 days) (P = 0.016). In contrast, no significant differences were observed in the mean and minimum NLR. A receiver-operating characteristic (ROC) analysis identified a maximum NLR cutoff of 4.3 for predicting early-onset hypothyroidism (P = 0.002, area under the curve (AUC) = 0.770). Conclusions A low baseline NLR was associated with hypothyroidism onset, and a persistently low NLR may contribute to early onset. These findings suggest that continuous NLR monitoring during pembrolizumab treatment may aid in predicting the risk of hypothyroidism and facilitate its appropriate management.
帕博利珠单抗是一种靶向程序性死亡-1（PD-1）/PD-1配体（PD-L1）的免疫检查点抑制剂，已显示出抗肿瘤作用，但可引起免疫相关不良事件（irAE），如甲状腺功能减退。中性粒细胞与淋巴细胞比值（NLR）可能与帕博利珠单抗疗效及irAE风险相关。本研究调查了NLR趋势与甲状腺功能减退发生之间的关系，评估其预测潜力。方法：本回顾性研究分析了2017年2月至2023年9月在日本东京慈惠会医科大学医院接受帕博利珠单抗治疗的136例晚期或复发性癌症患者。根据甲状腺功能减退的发生情况对患者进行分类，并比较其基线NLR和治疗失败时间（TTF）。还评估了甲状腺功能减退发作前的NLR趋势。根据发作时间（<90天与≥90天）对患者进一步分层，并比较发作前的NLR参数。结果：136例患者中有33例（24%）发生甲状腺功能减退。甲状腺功能减退组的基线NLR显著更低（P = 0.006），TTF更长（P = 0.006）。在甲状腺功能减退发作前未观察到显著的NLR变化（P = 0.626）。然而，早发型甲状腺功能减退（<90天）患者发作前的最大NLR显著更低（P = 0.016）。相比之下，平均NLR和最小NLR未观察到显著差异。受试者工作特征（ROC）分析确定预测早发型甲状腺功能减退的最大NLR临界值为4.3（P = 0.002，曲线下面积（AUC） = 0.770）。结论：低基线NLR与甲状腺功能减退发作相关，持续低NLR可能导致早发。这些发现表明，在帕博利珠单抗治疗期间持续监测NLR可能有助于预测甲状腺功能减退风险并促进其适当管理。
