BACKGROUND Immunotherapy with CTLA-4 inhibitors and PD1 checkpoint inhibitors has initiated a breakthrough in the treatment and prognosis of patients with metastatic melanoma. The survival of these patients has increased from the expected survival time of less than 12 months to at least forty months. However, immunotherapy with either anti-CTLA-4 antibodies or PD1 inhibitors alone or in combination has a broad palette of significant immune-related adverse events. The aim of the study was to assess the correlation of immune-related adverse events with treatment outcomes defined as significant differences in the overall response rate (ORR) and progression-free survival (PFS) of patients, who developed immune-related adverse events during immunotherapy. PATIENTS AND METHODS A retrospective analysis of patients with metastatic melanoma treated with immunotherapy in 2020 at the Oncology Institute of Ljubljana was performed. Only patients with radiological evaluation of the immunotherapy response were included. The patients were divided into two cohorts: a cohort of patients with immune-related adverse events (irAE group) and a cohort of patients with no immune-related adverse events (NirAE group). Significantly better overall response and progression-free survival in the irAE cohort defined the primary aim of our study. To investigate the differences in progression-free survival between the irAE cohort and NirAE cohort, we used survival analysis. In particular, a Cox proportional hazards model with covariates of time to progression and adverse events was used for survival analysis. The Kruskal-Wallis H-test was applied, and a p-value of p <= 0.05 was considered the cut-off point for a statistically significant difference between the groups. RESULTS Among the 120 patients treated with immunotherapy, radiological response evaluation was performed for 99 patients: 38 patients in the irAE cohort and 61 patients in the NirAE cohort. The ORRs for the irAE and NirAE cohorts were 57% and 37%, respectively. The PFS was significantly better for the irAE cohort (301.6 days) than for the NirAE cohort (247.29 days). The results of the survival regression analysis showed a significant increase in the survival probability from less than 60% for the NirAE cohort to almost 80% for the irAE cohort. CONCLUSIONS Patients with metastatic melanoma treated with immunotherapy who developed immune-related adverse events showed better treatment outcomes with longer times to disease progression and better overall response rates than patients treated with immunotherapy who did not develop immune-related adverse events, with a significant increase in the survival probability from less than 60% for the NirAE cohort to almost 80% for the irAE cohort.

中文翻译：

---

斯洛文尼亚转移性黑色素瘤患者免疫治疗期间的不良事件与更好的治疗结果呈正相关。


背景 CTLA-4抑制剂和PD1检查点抑制剂的免疫治疗在转移性黑色素瘤患者的治疗和预后方面取得了突破。这些患者的生存期从预计的不到12个月增加到至少四十个月。然而，单独或联合使用抗 CTLA-4 抗体或 PD1 抑制剂的免疫疗法会产生一系列重大的免疫相关不良事件。该研究的目的是评估免疫相关不良事件与治疗结果的相关性，治疗结果定义为在治疗期间发生免疫相关不良事件的患者的总体缓解率（ORR）和无进展生存期（PFS）的显着差异。免疫疗法。患者和方法对 2020 年在卢布尔雅那肿瘤研究所接受免疫治疗的转移性黑色素瘤患者进行了回顾性分析。仅纳入对免疫治疗反应进行放射学评估的患者。患者被分为两个队列：发生免疫相关不良事件的患者队列（irAE 组）和没有免疫相关不良事件的患者队列（NirAE 组）。 irAE 队列中显着更好的总体反应和无进展生存期确定了我们研究的主要目标。为了研究 irAE 队列和 NirAE 队列之间无进展生存期的差异，我们使用了生存分析。特别是，使用具有进展时间和不良事件协变量的 Cox 比例风险模型进行生存分析。应用 Kruskal-Wallis H 检验，p <= 0.05 的 p 值被认为是组间统计显着差异的分界点。 结果 在接受免疫治疗的 120 名患者中，对 99 名患者进行了放射学反应评估：38 名患者属于 irAE 队列，61 名患者属于 NirAE 队列。 irAE 和 NirAE 队列的 ORR 分别为 57% 和 37%。 irAE 队列（301.6 天）的 PFS 明显优于 NirAE 队列（247.29 天）。生存回归分析的结果显示，生存概率显着增加，从 NirAE 队列的不到 60% 增加到 irAE 队列的近 80%。结论 与未发生免疫相关不良事件的接受免疫治疗的患者相比，接受免疫治疗且出现免疫相关不良事件的转移性黑色素瘤患者表现出更好的治疗结果，疾病进展时间更长，总体缓解率更高，且生存概率从 NirAE 队列的低于 60% 增加到 irAE 队列的近 80%。