Department of Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
Faculty of information studies in Novo mesto, Novo mesto, Slovenia.
Radiol Oncol. 2021 May 4;55(3):354-361. doi: 10.2478/raon-2021-0019.
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.
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.
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.
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.
CTLA-4 抑制剂和 PD1 检查点抑制剂的免疫疗法在转移性黑色素瘤患者的治疗和预后方面开创了突破。这些患者的生存时间从预期的 12 个月以下增加到至少 40 个月。然而，单独使用抗 CTLA-4 抗体或 PD1 抑制剂或联合使用这两种药物，都具有广泛的显著免疫相关不良事件谱。本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，这些结果定义为在免疫治疗期间发生免疫相关不良事件的患者的总缓解率（ORR）和无进展生存期（PFS）的显著差异。
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。仅纳入了接受免疫治疗反应影像学评估的患者。将患者分为两组：发生免疫相关不良事件的患者队列（irAE 组）和未发生免疫相关不良事件的患者队列（NirAE 组）。irAE 队列中总缓解和无进展生存期显著改善，这是我们研究的主要目的。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 比例风险模型进行了生存分析。应用 Kruskal-Wallis H 检验，p 值<0.05 被认为是组间统计学差异的截止点。
在接受免疫治疗的 120 名患者中，对 99 名患者进行了影像学反应评估：irAE 队列 38 名患者，NirAE 队列 61 名患者。irAE 和 NirAE 队列的 ORR 分别为 57%和 37%。irAE 队列的 PFS 明显优于 NirAE 队列（301.6 天）。生存回归分析的结果表明，irAE 队列的生存概率从 NirAE 队列的不到 60%显著增加到 80%左右。
接受免疫治疗的转移性黑色素瘤患者发生免疫相关不良事件的患者，与未发生免疫相关不良事件的患者相比，具有更好的治疗结果，疾病进展时间更长，总缓解率更高，生存概率从 NirAE 队列的不到 60%显著增加到 irAE 队列的近 80%。
