Abstract
Background
Immune‐related adverse events (irAEs) have emerged as a serious clinical issue in the use of immune checkpoint inhibitors (ICIs). Risk factors for irAEs remain controversial. Therefore, we studied sex differences in irAEs in patients treated with anti‐programmed cell death protein 1 (PD‐1) therapy.
Materials and Methods
All patients with metastatic melanoma and non‐small cell lung cancer (NSCLC) treated with anti‐PD‐1 therapy at Mayo Clinic Rochester and Florida from 2015 to 2018 were reviewed. Kaplan‐Meier method and log‐rank test was used for time‐to‐event analysis.
Results
In 245 patients with metastatic melanoma, premenopausal women were more likely to experience irAEs (all grades) compared with postmenopausal women and men (67% vs. 60% vs. 46%), primarily because of an increase in endocrinopathies (33% vs. 12% vs. 10%, respectively). In patients with NSCLC (231 patients), women (all ages) were also more likely to develop irAEs of all grades (48% vs. 31%). Women with NSCLC were more likely to develop pneumonitis (11% vs. 4%) and endocrinopathies (14% vs. 5%). No differences in grade ≥3 toxicities were seen across sexes in both cohorts, but women were more likely to receive systemic steroids for the treatment of irAEs compared with men. Better progression‐free‐survival was observed in women with NSCLC and irAEs (10 months vs. 3.3 months) compared with women without irAEs.
Conclusion
Women with metastatic melanoma and NSCLC are more likely to experience irAEs compared with men. We also observed differences between sexes in the frequency of certain irAEs. Larger studies are needed to investigate the mechanisms underlying these associations.
Implications for Practice
The results of this study suggest that women may be at a higher risk for immune‐related adverse events (irAEs) compared with men when treated with anti‐programmed cell death protein 1 therapy. In addition, women were more likely to develop certain irAEs, including endocrinopathies and pneumonitis. Close follow‐up of women undergoing treatment with immune checkpoint inhibitors will allow clinicians to diagnose these treatment‐related complications early, potentially reducing their associated morbidity and mortality. In addition, a possible association between irAEs and response to therapy was observed.
摘要
背景。免疫相关不良事件 (irAE)在需要使用免疫检查点抑制剂 (ICI)时是一种严重的临床问题。有关 irAE 风险因素的讨论仍存在争议。因此，我们研究了采用抗程序性细胞死亡蛋白1 (PD‐1) 治疗患者的 irAE 性别差异。
材料和方法。本文回顾了 2015 年至 2018 年罗彻斯特与佛罗里达州梅奥诊所所有接受抗‐PD‐1 治疗的转移性黑色素瘤与非小细胞肺癌 (NSCLC) 患者的临床资料。采用 Kaplan‐Meier 法和时序检验法进行时间事件分析。
结果。245 例转移性黑色素瘤患者中，绝经前女性比绝经后女性和男性 (67% vs. 60% vs. 46%) 出现 irAE(所有等级)的可能性更高，主要原因为内分泌疾病的增加(分别为 33% vs. 12% vs. 10%)。NSCLC 患者中(231 例)，女性(所有年龄段)发生各种等级 irAE 的可能性更高 (48% vs. 31%)。NSCLC 女性患者出现肺炎 (11% vs. 4%) 和内分泌疾病 (14% vs. 5%) 的可能性更高。两组患者的 ≥3 级毒副反应未显示出性别上的差异，但女性因 irAE 而接受全身类固醇治疗的可能性较男性更高。NSCLC 并 irAE 女性患者的无进展生存期(10 个月 vs. 3.3 个月)优于无 irAE 的女性患者。
结论。转移性黑色素瘤和NSCLC的女性患者发生 irAE 的概率高于男性。结果还发现，某些 irAE 的频率在不同性别之间存在差异。需要更大规模的研究调查这些关联背后的机制。
实践意义:本项研究结果表明，与接受抗程序性细胞死亡蛋白 1 治疗的男性相比，女性发生免疫相关不良事件 (irAE) 的风险更高。此外，女性更容易出现内分泌疾病和肺炎等某些特定irAE。对接受免疫检查点抑制剂治疗的女性患者进行密切随访，有助于临床医生尽早诊断此类与治疗相关的并发症，从而降低相关病损率和死亡率。此外，结果显示，irAE 与治疗反应之间可能具有一定的关联。
This article reports on differences between men and women as related to immune‐related adverse events incidence and the potential link with response to therapy in patients with metastatic melanoma and non‐small cell lung cancer treated with anti‐PD1 agents.