In advanced cancer patients undergoing immune checkpoint blockade, the burden of immune-related adverse events (irAEs) is high. The need for reliable biomarkers for irAEs remains unfulfilled in this expanding therapeutic field. The lung immune prognostic index (LIPI) is a noninvasive measure of systemic inflammation that has consistently shown a correlation with survival in various cancer types when assessed at baseline. This study sought to determine whether early changes in the LIPI score could discriminate the risk of irAEs and different survival outcomes in advanced non-small cell lung cancer (NSCLC) patients receiving PD-(L)1 blockade-based therapies. We included consecutive patients diagnosed with metastatic NSCLC who received pembrolizumab, nivolumab, or atezolizumab as second-line therapy following platinum-based chemotherapy, or first-line pembrolizumab either alone or in combination with platinum-based chemotherapy. The LIPI score relied on the combined values of derived neutrophil/lymphocyte ratio (dNLR) and lactate dehydrogenase. Their assessment at baseline and after two cycles of treatment allowed us to categorize the population into three subgroups with good (LIPI-0), intermediate (LIPI-1), and poor (LIPI-2) prognosis. Between April 2016 and May 2023, we enrolled a total of 345 eligible patients, 165 (47.8%) and 180 (52.2%) of whom were treated as first- and second-line at our facility, respectively. After applying propensity score matching, we considered 83 relevant patients in each cohort with a homogeneous distribution of all characteristics across the baseline LIPI subgroups. There was a noticeable change in the distribution of LIPI categories due to a significant decrease in dNLR values during treatment. Although no patients shifted to a worse prognosis category, 20 (24.1%) transitioned from LIPI-1 to LIPI-0, and 7 (8.4%) moved from LIPI-2 to LIPI-1 (p< 0.001). Throughout a median observation period of 7.3 (IQR 3.9–15.1) months, a total of 158 irAEs (63.5%) were documented, with 121 (48.6%) and 39 (15.7%) patients experiencing mild to moderate and severe adverse events, respectively. Multivariate logistic regression analysis showed that the classification and changes in the LIPI score while on treatment were independent predictors of irAEs. The LIPI-0 group was found to have significantly increased odds of experiencing irAEs. Following a median follow-up period of 21.1 (95% CI 17.9–25.8) months, the multivariable Cox model confirmed LIPI categorization at any given time point as a significant covariate with influence on overall survival, irrespective of the treatment line. These findings suggest that reassessing the LIPI score after two cycles of treatment could help pinpoint patients particularly prone to immune-related toxicities. Those who maintain a good LIPI score or move from the intermediate to good category would be more likely to develop irAEs. The continuous assessment of LIPI provides prognostic insights and could be useful for predicting the benefit of PD-(L)1 checkpoint inhibitors.
在接受免疫检查点阻断治疗的晚期癌症患者中，免疫相关不良事件（irAEs）的发生负担较高。在这一不断扩展的治疗领域中，对irAEs可靠生物标志物的需求仍未得到满足。肺免疫预后指数（LIPI）是一种无创性全身炎症指标，基线评估时已在多种癌症类型中持续显示出与生存期的相关性。本研究旨在探讨LIPI评分的早期变化是否能够区分接受PD-(L)1阻断治疗的晚期非小细胞肺癌（NSCLC）患者发生irAEs的风险及不同生存结局。我们纳入了连续诊断为转移性NSCLC的患者，这些患者在接受铂类化疗后，将帕博利珠单抗、纳武利尤单抗或阿特珠单抗作为二线治疗，或接受一线帕博利珠单抗单药或联合铂类化疗。LIPI评分基于衍生中性粒细胞/淋巴细胞比值（dNLR）和乳酸脱氢酶的联合数值。在基线时和治疗两个周期后对其进行评估，使我们能够将人群分为预后良好（LIPI-0）、中等（LIPI-1）和不良（LIPI-2）三个亚组。2016年4月至2023年5月期间，我们共纳入345例符合条件的患者，其中165例（47.8%）和180例（52.2%）分别在我院接受一线和二线治疗。应用倾向评分匹配后，我们在每个队列中考虑了83例相关患者，所有特征在基线LIPI亚组中分布均匀。由于治疗期间dNLR值显著下降，LIPI类别的分布发生了明显变化。尽管没有患者转为更差的预后类别，但有20例（24.1%）从LIPI-1转为LIPI-0，7例（8.4%）从LIPI-2转为LIPI-1（p<0.001）。在中位观察期7.3（IQR 3.9–15.1）个月内，共记录了158例irAEs（63.5%），其中121例（48.6%）和39例（15.7%）患者分别经历了轻至中度和严重不良事件。多变量逻辑回归分析显示，治疗期间LIPI评分的分类和变化是irAEs的独立预测因子。研究发现LIPI-0组发生irAEs的几率显著增加。经过中位随访期21.1（95% CI 17.9–25.8）个月后，多变量Cox模型证实，在任何时间点的LIPI分类都是影响总生存期的显著协变量，且与治疗线数无关。这些发现表明，在两个周期的治疗后重新评估LIPI评分可能有助于识别特别容易发生免疫相关毒性的患者。那些维持良好LIPI评分或从中等转为良好类别的患者更有可能发生irAEs。LIPI的连续评估提供了预后见解，并可能有助于预测PD-(L)1检查点抑制剂的获益。
肿瘤(癌症)患者之家