Department of Medical Oncology, Cochin Hospital, AP-HP 5, CARPEM, CERTIM, Paris, France.
Department of Medical Oncology, Cochin Hospital, AP-HP 5, CARPEM, CERTIM, Paris, France.
Eur J Cancer. 2020 Jan;124:170-177. doi: 10.1016/j.ejca.2019.11.003. Epub 2019 Nov 30.
The occurrence of severe, acute limiting toxicity in patients receiving anti-programmed cell death receptor-1 monoclonal antibodies, such as nivolumab, is largely unpredictable. Sarcopenia was found to be associated with anti-cytotoxic T-lymphocyte-associated protein 4 acute toxicity. We explore the clinical and pharmacological parameters influencing nivolumab toxicity, including body composition.
From June 2015 to January 2017, all consecutive patients treated with nivolumab in our institution were prospectively included. We studied the relationship between muscle mass assessed by computed tomography, nivolumab trough level (C) at day 14 assessed using the enzyme-linked immunosorbent assay method, and the occurrence of immune grade III or IV toxicity or any toxicity leading to treatment discontinuation (immune-related acute limiting toxicity [irALT]).
In our population (n = 92) with a majority of lung cancer (72%), forty-five (51.7%) patients were sarcopenic. The median plasma nivolumab C at day 14 was 15.4 μg/mL (interquartile range = 11.8-21.0). In multivariate analysis, hypoalbuminaemia (<35 g/L) was independently associated with low nivolumab C on day 14 (odds ratio [OR] = 0.09; 95% confidence interval [CI] = 0.01-0.59, p = 0.01) and overweight/obesity with high nivolumab C on day 14 (OR = 5.94; 95% CI = 1.25-28.29, p = 0.03). We observed 22 irALTs in 19 patients (21%). The most frequent irALT was respiratory (6.5%) disorders and gastrointestinal (4.3%) disorders. Patients with sarcopenia were at significantly increased risk of experiencing an irALT (OR = 3.84; 95% CI = 1.02-14.46, p = 0.047). No association was found between toxicity and nivolumab plasma C at day 14.
Our results highlight the importance of assessing body composition and suggest that sarcopenia could predict severe immune-related toxicity of nivolumab in real life.
接受抗程序性细胞死亡受体-1 单克隆抗体（如 nivolumab）治疗的患者会发生严重的急性限制毒性，这种情况在很大程度上是不可预测的。肌少症与抗细胞毒性 T 淋巴细胞相关蛋白 4 急性毒性有关。我们探讨了影响 nivolumab 毒性的临床和药理学参数，包括身体成分。
从 2015 年 6 月至 2017 年 1 月，我们前瞻性地纳入了在我院接受 nivolumab 治疗的所有连续患者。我们研究了通过计算机断层扫描评估的肌肉量与第 14 天 nivolumab 谷浓度（C）之间的关系，该浓度使用酶联免疫吸附测定法进行评估，以及免疫 3 级或 4 级毒性或任何导致治疗中断的毒性（免疫相关急性限制毒性 [irALT]）的发生。
在我们的人群（n=92）中，大多数为肺癌（72%），45 名（51.7%）患者为肌少症患者。第 14 天的中位血浆 nivolumab C 为 15.4μg/mL（四分位间距=11.8-21.0）。在多变量分析中，低白蛋白血症（<35g/L）与第 14 天 nivolumab C 低有关（比值比[OR]为 0.09；95%置信区间[CI]为 0.01-0.59，p=0.01），超重/肥胖与第 14 天 nivolumab C 高有关（OR 为 5.94；95%CI 为 1.25-28.29，p=0.03）。我们观察到 19 名患者中有 22 例 irALT（21%）。最常见的 irALT 是呼吸系统（6.5%）和胃肠道（4.3%）疾病。肌少症患者发生 irALT 的风险显著增加（OR 为 3.84；95%CI 为 1.02-14.46，p=0.047）。第 14 天的 nivolumab 血浆 C 与毒性之间无相关性。
我们的结果强调了评估身体成分的重要性，并表明肌少症可能预测 nivolumab 严重的免疫相关毒性。
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