PURPOSE The metabolic changes associated with cachexia - sarcopenia syndrome might down-regulate antitumor immunity. We hypothesized that this syndrome reduces efficiency of immune checkpoint inhibitors (ICPI) in non-small cell lung cancer (NSCLC). METHODS The records of 142 consecutive NSCLC patients receiving first- or second-line anti-Programmed cell death protein 1) ICPI were reviewed. Response evaluation according to Response Evaluation Criteria in Solid Tumors 1.1 was performed at the eighth week of immunotherapy. Pretreatment cachexia was defined as a body-weight loss of 5% or more in the previous 6 months. Sarcopenia was estimated with the third lumbar skeletal muscle mass index (mSMI) and was evaluated before immunotherapy and at the eighth week. A decrease by 5% or more of the mSMI was considered as an evolving sarcopenia. The endpoints were disease control rate (DCR), progression-free (PFS) and overall survival (OS).Logistic regression model and Cox model took into account others covariables known to influence ICPI efficiency, particularly Programmed Death -Ligand 1 tumor cell score, Eastern Cooperative Oncology Group performance status and common somatic mutational status. RESULTS In multivariate analysis, cachexia - sarcopenia syndrome reduced the probability of achieving a disease control and were associated with a shorter survival. Patients without cachexia had a better probability to achieve disease control in comparison with those who did not experience cachexia (59.9 % and 41.1 %, respectively; odds ratio 95 % (confidence interval [95 %CI]): 2.60 (1.03-6.58)). Patients with cachexia had a shorter OS when compared with those without cachexia (hazard ratios [HR] (95 %CI): 6.26 (2.23-17.57)). Patients with an evolving sarcopenia had a shorter PFS and OS, with HR (95 %CI): 2.45 (1.09-5.53) and 3.87 (1.60-9.34) respectively. CONCLUSION Cachexia - sarcopenia syndrome negatively influences patients' outcome during anti-PD-1 ICPI therapy.

中文翻译：

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恶病质-肌肉减少症是接受免疫检查点抑制剂的非小肺癌患者疾病控制率和生存率的决定因素。

目的与恶病质-少肌症候群相关的代谢变化可能下调抗肿瘤免疫力。我们假设这种综合征降低了非小细胞肺癌（NSCLC）中免疫检查点抑制剂（ICPI）的效率。方法回顾性分析了142例连续接受一线或二线抗程序性细胞死亡蛋白1）ICPI的非小细胞肺癌患者的病历。在免疫治疗的第八周，根据实体瘤反应评估标准1.1进行反应评估。治疗前恶病质定义为在过去6个月中体重减轻5％或更多。肌肉减少症通过第三腰椎骨骼肌质量指数（mSMI）进行评估，并在免疫治疗之前和第八周进行评估。mSMI降低5％或更多被认为是进化性的肌肉减少症。终点为疾病控制率（DCR），无进展（PFS）和总生存期（OS）。Logistic回归模型和Cox模型考虑了已知会影响ICPI效率的其他协变量，特别是程序性死亡-配体1肿瘤细胞评分，东部合作肿瘤小组的表现状态和常见的体细胞突变状态。结果在多变量分析中，恶病质-少肌症候群降低了实现疾病控制的可能性，并与较短的生存期相关。与没有恶病质的患者相比，没有恶病质的患者更有可能实现疾病控制（分别为59.9％和41.1％；优势比为95％（置信区间[95％CI]）：2.60（1.03-6.58）） 。与没有恶病质的患者相比，恶病质的患者的OS短（危险比[HR]（95％CI）：6.26（2.23-17.57））。肌肉减少症患者的PFS和OS较短，HR（95％CI）分别为2.45（1.09-5.53）和3.87（1.60-9.34）。结论恶病质-肌肉减少症综合征在抗PD-1 ICPI治疗期间对患者的预后产生负面影响。