Quality of life and mental health in real-world patients with resected stage III/IV melanoma receiving adjuvant immunotherapy

Treatment with immune checkpoint inhibitors (ICI) has expanded into the adjuvant setting enhancing the importance of knowledge on the immune-related toxicities and their impact on health-related quality of life (HRQoL). Large phase 3 trials of patients with resected Stage III/IV melanoma found no effect on HRQoL during adjuvant immunotherapy. This study investigates how HRQoL was affected during and after adjuvant immunotherapy in a real-world setting. Patients with resected melanoma treated with adjuvant nivolumab from 2018 to 2021 in Denmark were identified using the Danish Metastatic Melanoma Database (DAMMED). The study was performed as a nationwide cross-sectional analysis as a questionnaire consisting of six different validated questionnaires on HRQoL, cognitive function, fatigue, depression, fear of recurrence, and decision regret was sent to all patients in March 2021. To evaluate HRQoL during and after adjuvant treatment, patients were divided into groups depending on their treatment status when answering the questionnaire; patients in active treatment for 0–6 months, patients in active treatment for >6 months, patients who ended treatment 0–6 months ago, and patients who ended treatment >6 months ago. A total of 271/412 (66%) patients completed the questionnaire. Patients who ended therapy 0–6 months ago had the lowest HRQoL and had more fatigue. Patients in active treatment for >6 months had lower HRQoL and more fatigue than patients who started treatment 0–6 months ago. Patients ending therapy >6 months ago had higher HRQoL and less fatigue compared to patients who ended therapy 0–6 months ago. Multivariable analysis showed an association between HRQoL and treatment status, comorbidity, civil status, and employment status. Adjuvant nivolumab may affect some aspects of QoL, but the influence seems temporary. Patient characteristics, such as civil status, employment status, and comorbidity were associated with HRQoL.

免疫检查点抑制剂（immune checkpoint inhibitors, ICI）的治疗应用已拓展至辅助治疗场景，使得免疫相关不良反应及其对健康相关生活质量（health-related quality of life, HRQoL）的临床认知重要性显著提升。既往针对切除术后III/IV期黑色素瘤患者的大型III期临床试验显示，辅助免疫治疗期间患者的HRQoL未受明显影响。本研究旨在探究真实世界环境中，辅助免疫治疗期间及治疗结束后患者的HRQoL变化情况。本研究纳入2018至2021年在丹麦接受辅助纳武利尤单抗治疗的切除术后黑色素瘤患者，数据提取自丹麦转移性黑色素瘤数据库（Danish Metastatic Melanoma Database, DAMMED）。研究采用全国性横断面分析设计：于2021年3月向所有符合条件的患者发放问卷，问卷包含6种经过效度验证的评估工具，分别用于评估HRQoL、认知功能、疲劳、抑郁、复发恐惧及决策后悔。为评估辅助治疗期间及治疗结束后的HRQoL，研究根据患者填写问卷时的治疗状态进行分组：接受活动性治疗0~6个月组、接受活动性治疗＞6个月组、治疗结束0~6个月组及治疗结束＞6个月组。最终共有271/412（66%）的患者完成问卷填写。分析结果显示：治疗结束0~6个月的患者HRQoL最低，且疲劳症状更为显著；接受治疗＞6个月的患者较接受治疗0~6个月的患者，HRQoL更低、疲劳程度更重；治疗结束＞6个月的患者较治疗结束0~6个月的患者，HRQoL更高、疲劳程度更轻。多变量分析表明，HRQoL与治疗状态、合并症、婚姻状况及就业状况存在独立相关性。辅助纳武利尤单抗治疗可能对生活质量的部分维度产生影响，但该影响似乎具有一过性。患者的婚姻状况、就业状况及合并症等临床特征与HRQoL存在显著关联。