Zhang Wei-Hong, Li Bing-Xue, Ma Chen-Xi, Wang Jian, Yang Fan, Xiong Yan-Juan, Li Shu-Zhan, Zhang Jia-Li, Du Wei-Jiao, Hui Zhen-Zhen, Shen Meng, Zhou Li, Li Run-Mei, Tian Xiao, Han Ying, Ren Bao-Zhu, Ichiki Yoshinobu, Lee Sang Chul, Zhang Xin-Wei, Cao Shui, Ren Xiu-Bao, Liu Liang
Department of Immunology and Biotherapy, Key Laboratory of Cancer Immunology and Biotherapy, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Department of General Thoracic Surgery, Saitama Medical Center, Hidaka, Japan.
Transl Lung Cancer Res. 2024 Oct 31;13(10):2787-2801. doi: 10.21037/tlcr-24-795. Epub 2024 Oct 28.
Antihistamines alleviate the side effects of antitumor drugs and exert antitumor effects. This study aimed to investigate the potential impact of short-term concomitant use of antihistamines with immune checkpoint inhibitor (ICI) therapy on the efficacy and immune-related adverse events (irAEs) of immunotherapy for patients with advanced lung cancer.
We retrospectively analyzed the medical records of 211 patients diagnosed with advanced primary lung cancer and treated with immunotherapy at Tianjin Medical University Cancer Institute and Hospital between January 1, 2018, and January 1, 2022. Among these patients, 109 who received H1 antihistamine during the infusion of anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) antibodies were assigned to the experimental group; meanwhile, the remaining 102 patients who did not receive H1 antihistamines were assigned to the control group. Balancing was achieved through inverse probability of treatment weight (IPTW) estimation. The data were analyzed using Kaplan-Meier curves and Cox regression analyses.
The median progression-free survival (mPFS) was 12.7 months in the experimental group and 4.3 months in the control group, while the median overall survival (mOS) was 32.8 months in the experimental group and 18.1 months in the control group. In the experimental group, patients treated with only H1 antihistamines had longer mPFS and mOS compared with those who received H1 plus H2 antihistamines. Similarly, in the control group, patients who did not receive antihistamines had a longer mPFS and mOS than those who only received H2 antihistamines. After conducting multivariate analyses, we found that H1 and H2 antihistamines were respectively identified as good and poor independent prognostic factors for both progression-free survival (PFS) and overall survival (OS). The rates of irAEs in the experimental and control groups were 52.4% and 69.2%, respectively, and grade ≥3 irAEs occurred in 4.5% and 25.9% of patients, respectively.
Concomitant use of H1 antihistamines can improve immunotherapy efficacy and reduce irAEs. Meanwhile, concomitant use of H2 antihistamines is associated with reduced PFS and OS time.
抗组胺药可减轻抗肿瘤药物的副作用并发挥抗肿瘤作用。本研究旨在探讨短期联合使用抗组胺药与免疫检查点抑制剂（ICI）治疗对晚期肺癌患者免疫治疗疗效和免疫相关不良事件（irAEs）的潜在影响。
我们回顾性分析了2018年1月1日至2022年1月1日期间在天津医科大学肿瘤医院被诊断为晚期原发性肺癌并接受免疫治疗的211例患者的病历。在这些患者中，109例在输注抗程序性细胞死亡蛋白1（PD-1）和抗程序性细胞死亡配体1（PD-L1）抗体期间接受H1抗组胺药治疗的患者被分配到实验组；同时，其余102例未接受H1抗组胺药治疗的患者被分配到对照组。通过治疗权重的逆概率（IPTW）估计实现平衡。使用Kaplan-Meier曲线和Cox回归分析对数据进行分析。
实验组的中位无进展生存期（mPFS）为12.7个月，对照组为4.3个月，而实验组的中位总生存期（mOS）为32.8个月，对照组为18.1个月。在实验组中，仅接受H1抗组胺药治疗的患者的mPFS和mOS比接受H1加H2抗组胺药治疗的患者更长。同样，在对照组中，未接受抗组胺药治疗的患者的mPFS和mOS比仅接受H2抗组胺药治疗的患者更长。在进行多变量分析后，我们发现H1和H2抗组胺药分别被确定为无进展生存期（PFS）和总生存期（OS）的良好和不良独立预后因素。实验组和对照组的irAEs发生率分别为52.4%和69.2%，≥3级irAEs分别发生在4.5%和25.9%的患者中。
联合使用H1抗组胺药可提高免疫治疗疗效并减少irAEs。同时，联合使用H2抗组胺药与PFS和OS时间缩短有关。
