全身类固醇通常用于控制免疫相关不良事件 (irAE)，但目前尚不清楚它们是否会损害免疫检查点抑制剂 (ICI) 的治疗效果。很少有研究评估类固醇用药时机的影响及其与继续或停止 ICI 治疗的关系。旨在描述全身类固醇和 irAE 的类固醇用药时机与接受 ICI 治疗的患者的生存率之间的关系。这项多中心回顾性队列研究涵盖了接受 ICI 治疗的退伍军人2010年1月1日至2021年12月31日之间的癌症。数据分析于2023年9月8日进行。可识别的癌症初步诊断。患者被分为 3 组：未接受类固醇治疗的患者、针对 irAE 接受全身类固醇治疗的患者以及因非 irAE 相关原因而接受类固醇治疗的患者。所有符合条件的患者均接受 1 剂或多剂 ICI（atezolizumab、avelumab、cemiplimab、durvalumab、ipilimumab、nivolumab 或 pembrolizumab）。类固醇组中符合条件的患者接受至少 1 剂（静脉内、肌肉内或口服）地塞米松、氢化可的松、甲泼尼龙、泼尼松或泼尼松龙。基线时使用类固醇用于姑息治疗或输注预防或作为单剂量给药被认为与irAE无关。所有其他类固醇使用模式均被假定为针对 irAE。主要结局是总体生存率，并在 ICI 启动后进行 5 年随访。通过成对时序检验进行 Kaplan-Meier 生存分析以确定显着性。采用 Cox 比例风险回归对风险进行建模。队列由 20163 名接受 ICI 治疗的退伍军人组成，其中包括 12221 名患者（平均 [SD] 年龄，69.5 [8.0] 岁；11830 名男性患者 [96.8%]；9394 名白人患者 [76.9]。 ％]）在 ICI 治疗期间接受全身类固醇治疗的患者和 7942 名未接受全身类固醇治疗的患者（平均 [SD] 年龄，70.3 [8.5] 岁；7747 名男性患者 [97.5%]；6085 名白人患者 [76.6%]）。与未诊断出 irAE 的患者相比，诊断出 irAE 的患者总生存期 (OS) 显着改善（中位 [IQR] OS 为 17.4 [6.6 至 48.5] 个月 vs 10.5 [3.5 至 36.8] 个月；调整后风险比，0.84；95% CI， 0.81-0.84；P < .001)。对于 irAE 患者，与因非 irAE 相关原因接受类固醇治疗或未接受类固醇治疗的患者相比，针对 irAE 的全身类固醇治疗与生存率显着改善相关（中位 [IQR] OS 为 21.3 [9.3 至 58.2] 个月 vs 13.6 [5.5] 个月至 33.7] 个月 vs 15.8 [4.9 至未达到] 个月；P <.001)。然而，在那些因 irAE 接受类固醇治疗的患者中，与后期使用类固醇相比，早期使用类固醇（ICI 开始后 <2 个月）与相对生存获益降低相关，无论 ICI 是否继续或在类固醇开始后停止（ICI 后中位 [IQR] OS）停止治疗 4.4 [1.9 至 19.5] 个月 vs 16.0 [8.0 至 42.2] 个月；继续 ICI 后中位 [IQR] OS，16.0 [7.1 至未达到] 个月 vs 29.2 [16.5 至 53.5] 个月；P <.001）。研究表明，用于 irAE 管理的类固醇可能不会消除与 irAE 相关的生存获益。然而，尽管继续进行 ICI 治疗，但在 ICI 开始后 2 个月内早期给予类固醇与较短的生存期相关。

Systemic steroids are commonly used to manage immune-related adverse events (irAEs), but it remains unclear whether they may undermine immune checkpoint inhibitor (ICI) therapy outcomes. Few studies have assessed the impact of steroid timing and its association with continuation or cessation of ICI therapy.To characterize how systemic steroids and steroid timing for irAEs are associated with survival in patients receiving ICI therapy.This multicenter retrospective cohort study encompassed veterans receiving ICI for cancer between January 1, 2010, and December 31, 2021. Data analysis was conducted September 8, 2023.Identifiable primary diagnosis of cancer. Patients were categorized into 3 cohorts: those receiving no steroids, systemic steroids for irAEs, and steroids for non-irAE-associated reasons. All eligible patients received 1 or more doses of an ICI (atezolizumab, avelumab, cemiplimab, durvalumab, ipilimumab, nivolumab, or pembrolizumab). Eligible patients in the steroid group received at least 1 dose (intravenous, intramuscular, or oral) of dexamethasone, hydrocortisone, methylprednisolone, prednisone, or prednisolone. Steroid use at baseline for palliation or infusion prophylaxis or delivered as a single dose was deemed to be non-irAE associated. All other patterns of steroid use were assumed to be for irAEs.The primary outcome was overall survival, with a 5-year follow-up after ICI initiation. Kaplan-Meier survival analyses were performed with pairwise log-rank tests to determine significance. Risk was modeled with Cox proportional hazard regression.The cohort consisted of 20 163 veterans receiving ICI therapy including 12 221 patients (mean [SD] age, 69.5 [8.0] years; 11 830 male patients [96.8%]; 9394 White patients [76.9%]) who received systemic steroids during ICI treatment and 7942 patients (mean [SD] age, 70.3 [8.5] years; 7747 male patients [97.5%]; 6085 White patients [76.6%]) who did not. Patients with an irAE diagnosis had significantly improved overall survival (OS) compared with those without (median [IQR] OS, 17.4 [6.6 to 48.5] months vs 10.5 [3.5 to 36.8] months; adjusted hazard ratio, 0.84; 95% CI, 0.81-0.84; P < .001). For patients with irAEs, systemic steroids for irAEs were associated with significantly improved survival compared with those who received steroids for non-irAE-related reasons or no steroid treatment (median [IQR] OS, 21.3 [9.3 to 58.2] months vs 13.6 [5.5 to 33.7] months vs 15.8 [4.9 to not reached] months; P <.001). However, among those who received steroids for irAEs, early steroid use (<2 months after ICI initiation) was associated with reduced relative survival benefit vs later steroid use, regardless of ICI continuation or cessation following steroid initiation (median [IQR] OS after ICI cessation 4.4 [1.9 to 19.5] months vs 16.0 [8.0 to 42.2] months; median [IQR] OS after ICI continuation, 16.0 [7.1 to not reached] months vs 29.2 [16.5 to 53.5] months; P <.001).This study suggests that steroids for irAE management may not abrogate irAE-associated survival benefits. However, early steroid administration within 2 months of ICI initiation is associated with shorter survival despite continuation of ICI therapy.