Background: The effects of steroid-sparing immunosuppressive agents (SSIAs), used for the treatment of immune-related adverse events (irAEs), on immune checkpoint inhibitor (ICI) antitumor activity is not well known. We compared tumor outcomes of patients who received corticosteroid monotherapy (CS) versus a corticosteroid plus SSIA (CS-SSIA) for irAE treatment, using statistical methods to address immortal time bias. Methods: We conducted a retrospective case-control study on patients ≥ 18 years with melanoma or non-small-cell lung cancer (NSCLC) treated with ≥1 ICI at a quaternary care center between 1 January 2016 and 11 January 2021. Patients were divided into two cohorts: CS or CS-SSIA. We used propensity score nearest-neighbor matching to match on tumor type, stage, and prior lines of therapy. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included the time from the start of the irAE treatment to the irAE resolution. Hazard ratios (HRs) for PFS and OS were calculated using the Cox proportional hazard regression method with both (1) the time to the steroid and SSIA as time-varying covariates and (2) a binary exposure classification not accounting for the time to the treatment. Results: A total of 167 patients were included after matching (132 in the CS cohort and 35 in the CS-SSIA cohort). Sixty-six percent of all the patients had melanoma. The most common irAEs requiring treatment were gastroenterocolitis and hepatitis. In an adjusted analysis not accounting for immortal time bias, there were no significant differences in PFS (HR 0.75, 95% CI [0.46–1.23]) or OS (HR 0.82, 95% CI [0.46–1.47]). In analyses using a time-varying treatment indicator, there was a trend toward improved PFS in patients treated with SSIAs (HR 0.54, CI 0.26–1.10). There was no difference in OS (HR 1.11, CI 0.55–2.23). Patients with melanoma who specifically received infliximab had improved PFS compared to patients with CS only, after adjusting for immortal time bias (HR 0.32, CI 0.24–0.43). Conclusions: The use of SSIAs with CS did not have worse outcomes than CS monotherapy. In melanoma, our findings showed improved PFS for the use of infliximab versus steroid monotherapy for irAEs. Large, prospective, randomized controlled trials are needed to confirm these findings and guide the optimal treatment of irAEs.
背景：用于治疗免疫相关不良事件（irAEs）的类固醇节约型免疫抑制剂（SSIAs）对免疫检查点抑制剂（ICI）抗肿瘤活性的影响尚不明确。本研究比较了接受皮质类固醇单药治疗（CS）与皮质类固醇联合SSIA治疗（CS-SSIA）的irAE患者的肿瘤结局，并采用统计学方法处理了不朽时间偏倚。 方法：我们对2016年1月1日至2021年1月11日期间在一家四级医疗中心接受≥1种ICI治疗的、年龄≥18岁的黑色素瘤或非小细胞肺癌（NSCLC）患者进行了一项回顾性病例对照研究。患者被分为两个队列：CS组或CS-SSIA组。我们使用倾向评分最近邻匹配法，根据肿瘤类型、分期和既往治疗线数进行匹配。主要结局是无进展生存期（PFS）和总生存期（OS）。次要结局包括从开始irAE治疗到irAE缓解的时间。使用Cox比例风险回归模型计算PFS和OS的风险比（HR），采用两种方法：（1）将使用类固醇和SSIA的时间作为时变协变量；（2）使用未考虑治疗开始时间的二元暴露分类。 结果：匹配后共纳入167例患者（CS队列132例，CS-SSIA队列35例）。所有患者中66%患有黑色素瘤。需要治疗的最常见irAEs是胃肠结肠炎和肝炎。在未校正不朽时间偏倚的分析中，PFS（HR 0.75，95% CI [0.46–1.23]）或OS（HR 0.82，95% CI [0.46–1.47]）均无显著差异。在使用时变治疗指标的分析中，接受SSIA治疗的患者PFS有改善趋势（HR 0.54，CI 0.26–1.10）。OS无差异（HR 1.11，CI 0.55–2.23）。在校正不朽时间偏倚后，与仅接受CS治疗的患者相比，特定接受英夫利西单抗治疗的黑色素瘤患者PFS有所改善（HR 0.32，CI 0.24–0.43）。 结论：CS联合SSIA治疗并未比CS单药治疗产生更差的结局。在黑色素瘤中，我们的研究结果显示，与类固醇单药治疗相比，使用英夫利西单抗治疗irAEs可改善PFS。需要进行大规模、前瞻性、随机对照试验来证实这些发现，并指导irAEs的最佳治疗。
肿瘤(癌症)患者之家