BACKGROUND Gut microbial diversity is associated with improved response to immune checkpoint inhibitors (ICI). Based on the known detrimental impact that antibiotics have on microbiome diversity, we hypothesized that antibiotic receipt prior to ICI would be associated with decreased survival. METHODS Patients with stage III and IV melanoma treated with ICI between 2008 and 2019 were selected from an institutional database. A window of antibiotic receipt within 3 months prior to the first infusion of ICI was pre-specified. The primary outcome was overall survival (OS) and secondary outcomes were melanoma-specific mortality and immune-mediated colitis requiring intravenous (IV) steroids. All statistical tests were two-sided. RESULTS There were 568 patients in our database, of which 114 received antibiotics prior to ICI. 35.9% of patients had stage III disease. On multivariable Cox proportional hazards analysis of patients with stage IV disease, the antibiotic-exposed group had statistically significantly worse OS (hazard ratio [HR] 1.81, 95% confidence interval [CI] 1.27-2.57, p<.001). The same effect was observed among antibiotic-exposed patients with stage III disease (HR 2.78, 95% CI 1.31-5.87, p=.007). When limited to only patients who received adjuvant ICI (N = 89), antibiotic-exposed patients also had statistically significantly worse OS (HR 4.84, 95% CI 1.09-21.50, p=.04). The antibiotic group had a greater incidence of colitis (HR 2.14, 95% CI 1.02-4.52, p=.046). CONCLUSION Patients with stage III and IV melanoma exposed to antibiotics prior to ICI had statistically significantly worse OS than unexposed patients. Antibiotic exposure was associated with greater incidence of moderate to severe immune-mediated colitis. Given the large number of antibiotics prescribed annually, physicians should be judicious with their use in cancer populations likely to receive ICI.

中文翻译：

---

在接受免疫治疗的黑色素瘤患者中，抗生素暴露与生存和毒性的关系。

背景 肠道微生物多样性与改善对免疫检查点抑制剂 (ICI) 的反应有关。基于已知的抗生素对微生物组多样性的不利影响，我们假设在 ICI 之前接受抗生素会降低生存率。方法 从机构数据库中选择 2008 年至 2019 年间接受 ICI 治疗的 III 期和 IV 期黑色素瘤患者。预先指定了在首次输注 ICI 前 3 个月内接受抗生素的窗口。主要结果是总生存期 (OS)，次要结果是黑色素瘤特异性死亡率和需要静脉注射 (IV) 类固醇的免疫介导结肠炎。所有统计测试都是双向的。结果 我们的数据库中有 568 名患者，其中 114 名患者在 ICI 前接受了抗生素治疗。35. 9% 的患者患有 III 期疾病。在 IV 期疾病患者的多变量 Cox 比例风险分析中，抗生素暴露组的 OS 显着更差（风险比 [HR] 1.81，95% 置信区间 [CI] 1.27-2.57，p<.001）。在使用抗生素的 III 期疾病患者中观察到相同的效果（HR 2.78, 95% CI 1.31-5.87, p=.007）。当仅限于接受辅助 ICI 的患者 (N = 89) 时，抗生素暴露患者的 OS 也有统计学意义的更差 (HR 4.84, 95% CI 1.09-21.50, p=.04)。抗生素组的结肠炎发生率更高（HR 2.14, 95% CI 1.02-4.52, p=.046）。结论 在 ICI 之前暴露于抗生素的 III 期和 IV 期黑色素瘤患者的 OS 比未暴露的患者在统计学上显着更差。抗生素暴露与中度至重度免疫介导结肠炎的发病率增加有关。鉴于每年开出大量抗生素，医生应该谨慎地将其用于可能接受 ICI 的癌症人群。