Nardone Valerio, Giannicola Rocco, Bianco Giovanna, Giannarelli Diana, Tini Paolo, Pastina Pierpaolo, Falzea Antonia Consuelo, Macheda Sebastiano, Caraglia Michele, Luce Amalia, Zappavigna Silvia, Mutti Luciano, Pirtoli Luigi, Giordano Antonio, Correale Pierpaolo
Unit of Radiation Oncology, Ospedale del Mare, Naples, Italy.
Medical Oncology Unit, Grand Metropolitan Hospital "Bianchi-Melacrino-Morelli", Reggio Calabria, Italy.
Front Oncol. 2021 Jun 14;11:684110. doi: 10.3389/fonc.2021.684110. eCollection 2021.
Peripheral-immune-checkpoint blockade (P-ICB) with mAbs to PD-1 (nivolumab and pembrolizumab) or PD-L1 (atezolizumab, durvalumab, avelumab) alone or combination with chemotherapy represents a novel active treatment for mNSCLC patients. However, this therapy can be associated to immune-related adverse events (irAEs) and high cost. Therefore, finding reliable biomarkers of response and irAEs is strongly encouraged to accurately select patients who may potentially benefit from the immuno-oncological treatment. This is a retrospective multi-institutional analysis performed on ninety-five mNSCLC patients who received real-world salvage therapy with nivolumab or atezolizumab between December 2015 and April 2020. The outcome of these patients in term of PFS and OS was evaluated in comparison with different serum levels of C-reactive protein (CRP), Erythrocyte Sedimention Rate (ESR) and Procalcitonin (PCT) by performing Kaplan-Meier and Log-rank test and multivariate analysis. We found that high baseline levels of CRP, ESR, and PCT were strongly predictive of poor outcome (P <0.05) with the worse prognosis detected in those patients with a baseline levels of both ESR and PCT over the pre-established cut off (median OS recorded in patients with no marker over the cut off . those with just one marker over the cut off . those with both markers over the cut off: 40 ± 59 . 15.5 ± 5.5 . 5.5 ± 1.6 months, respectively; P <0.0001). Our results suggest the predictive value of systemic inflammation and suggest a potential role of PCT in predicting a poor outcome in mNSCLC receiving PD-1/PD-L1 blocking mAbs. This finding also suggests a potential role of subclinical bacterial infections in defining the response to PD-1/PD-L1 blocking mAbs that deserves further and more specific investigations.
使用抗PD-1单克隆抗体（纳武单抗和派姆单抗）或抗PD-L1单克隆抗体（阿特珠单抗、度伐鲁单抗、阿维鲁单抗）进行外周免疫检查点阻断（P-ICB），单独或与化疗联合使用，是晚期非小细胞肺癌（mNSCLC）患者的一种新型有效治疗方法。然而，这种治疗可能会伴有免疫相关不良事件（irAE）且成本高昂。因此，强烈鼓励寻找可靠的反应和irAE生物标志物，以准确选择可能从免疫肿瘤治疗中获益的患者。这是一项回顾性多机构分析研究，对95例在2015年12月至2020年4月期间接受纳武单抗或阿特珠单抗实际挽救治疗的mNSCLC患者进行。通过Kaplan-Meier法、对数秩检验和多变量分析，比较这些患者不同血清水平的C反应蛋白（CRP）、红细胞沉降率（ESR）和降钙素原（PCT），评估其无进展生存期（PFS）和总生存期（OS）的结果。我们发现，CRP、ESR和PCT的高基线水平强烈预示着预后不良（P<0.05），ESR和PCT基线水平均超过预先设定临界值的患者预后更差（无标志物超过临界值的患者、仅有一个标志物超过临界值的患者、两个标志物均超过临界值的患者的中位OS分别为：40±59、15.5±5.5、5.5±1.6个月；P<0.0001）。我们的结果表明全身炎症具有预测价值，并提示PCT在预测接受PD-1/PD-L1阻断单克隆抗体治疗的mNSCLC患者预后不良方面可能发挥作用。这一发现还提示亚临床细菌感染在确定对PD-1/PD-L1阻断单克隆抗体的反应中可能发挥作用，值得进一步进行更具体的研究。
