BACKGROUND Several studies have found an association between higher body mass index (BMI) and improved clinical outcomes in cancer patients receiving programmed cell death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) checkpoint inhibitors. In a previous study, we found that overweight/obese patients were significantly more likely to experience any grade immune-related adverse events (irAEs) compared to non-overweight patients. PATIENTS AND METHODS We conducted a 'real-life', multi centre, retrospective observational study aimed at comparing the incidence of irAEs among cancer patients treated with PD-1/PD-L1 inhibitors according to baseline BMI. RESULTS One thousand and seventy advanced cancer patients were evaluated. The median age was 68 years (range: 21-92), male/female ratio was 724/346. Primary tumours were: non-small-cell lung carcinoma (NSCLC) (653 patients), melanoma (233 patients), renal cell carcinoma (RCC) (152 patients) and others (29 patients). Median BMI was 25 (13.6-46.6); according to World Health Organisation (WHO) classification, 44 patients (4.1%) were defined as underweight, 480 patients (44.9%) as having a normal weight, 416 patients (38.9%) as overweight and 130 patients (12.1%) as obese. Higher BMI was significantly related to higher occurrence of any grade immune-related adverse events [irAEs] (p < 0.0001), G3/G4 irAEs (p < 0.0001) and irAEs leading to discontinuation (LTD) (p < 0.0001). Overweight and obesity were confirmed predictors for irAEs of any grade at both univariate and multivariate analysis. The adjusted odds ratios (ORs) (compared to normal-weight) were 10.6; 95% confidence interval (95%CI): 7.5-14.9 for overweight, and 16.6 (95%CI: 10.3-26.7) for obese patients. Obesity was the only factor significantly related to a higher incidence of G3/G4 irAEs (OR = 11.9 [95%CI: 6.4-22.3], p < 0.0001) and LTD irAEs (OR = 8.8 [95%CI: 4.3-18.2], p < 0.0001). Overweight and obese patients experienced a significantly higher occurrence of cutaneous, endocrine, gastro-intestinal (GI), hepatic and 'others' irAEs, compared to normal-weight patients. Only obese patients experienced a significantly higher occurrence of pulmonary and rheumatic irAEs, compared to normal-weight patients. CONCLUSIONS Considering the previously evidenced association between higher BMI and better outcome, the current finding about the relationship between BMI and irAEs occurrence can contribute to consideration of these findings as the upside of the downside, which underlies an 'immunogenic phenotype'.

中文翻译：

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体重指数（BMI）与接受程序性细胞死亡蛋白1（PD-1）/程序性细胞死亡配体1（PD-L1）检查点抑制剂的癌症患者的临床结局之间的关联的另一方面：免疫的多中心分析相关的不良事件。

背景技术几项研究发现，在接受程序性细胞死亡蛋白-1（PD-1）/程序性细胞死亡配体1（PD-L1）检查点抑制剂的癌症患者中，较高的体重指数（BMI）与改善的临床结局之间存在关联。在先前的研究中，我们发现与非超重患者相比，超重/肥胖患者更有可能发生任何等级的免疫相关不良事件（irAE）。患者和方法我们进行了一项“真实”，多中心，回顾性观察性研究，旨在根据基线BMI比较接受PD-1 / PD-L1抑制剂治疗的癌症患者中irAE的发生率。结果对177例晚期癌症患者进行了评估。中位年龄为68岁（范围：21-92岁），男女比例为724/346。原发性肿瘤为：非小细胞肺癌（NSCLC）（653例），黑素瘤（233例），肾细胞癌（RCC）（152例）和其他（29例）。BMI中位数为25（13.6-46.6）；根据世界卫生组织（WHO）的分类，体重不足的定义为44例（4.1％），体重正常的定义为480例（44.9％），肥胖为416例（38.9％），肥胖为130例（12.1％） 。较高的BMI与任何等级的免疫相关不良事件[irAEs]（p <0.0001），G3 / G4 irAEs（p <0.0001）和irAEs导致停药（LTD）（p <0.0001）的发生率显着相关。在单变量和多变量分析中，超重和肥胖是任何级别的irAE的预测指标。调整后的优势比（OR）（与正常体重相比）为1​​0.6；95％置信区间（95％CI）：7.5-14。超重为9，肥胖患者为16.6（95％CI：10.3-26.7）。肥胖是与G3 / G4 irAEs（OR = 11.9 [95％CI：6.4-22.3]，p <0.0001）和LTD irAEs（OR = 8.8 [95％CI：4.3-18.2] ，p ＜0.0001）。与正常体重的患者相比，超重和肥胖的患者发生皮肤，内分泌，胃肠（GI），肝和“其他” irAE的发生率显着增加。与正常体重的患者相比，只有肥胖的患者发生肺和风湿性irAE的发生率明显更高。结论考虑到先前证明的BMI较高与预后较好之间的关联，目前有关BMI与irAE发生之间关系的发现可能有助于将这些发现视为不利因素，